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Biomedical subjects

M Schilling

Publications and source records attributed to M Schilling.

At least 37 records · Page 2Linked to original sources

Fundus rotation gastroplasty: rationale, technique and results.

Anastomotic leakage is the main factor (up to 30%) for postoperative morbidity and mortality after esophageal resection. Compromised anastomotic perfusion after dissection of supplying vessels for gastric tube formation and tension on the suture line are the two main reasons for anastomotic insufficiency. To prevent anastomotic leakage, a new technique for gastric tube formation after esophageal resection has been developed and introduced into surgical practice: the fundus rotation gastroplasty (FRG). The following paper summarizes rationale, technique and early results of this new technique. It is shown that the FRG is a safe and effective technique for esophageal reconstruction and offers important advantages over conventional gastroplasties: (i). the improved perfusion of the oral part of the tube; (ii). the gain of tube length allowing for a safer performance of even pharyngeal anastomosis as shown by the low insufficiency rate of 9%; and (iii). the increase of remaining gastric reservoir supporting physiologic stomach and gut function. Therefore, the FRG seems to be an alternative and safe method for esophageal reconstruction, especially for high anastomotic locations.

Anastomosis, Surgical↗

Expression of CD44v6 has no prognostic value in patients with colorectal cancer.

BACKGROUND AND AIMS: In colorectal cancer patients' mortality is largely influenced by spreading of tumour cells from the primary tumour site and subsequent metastasis formation. CD44 is an adhesion molecule and represents a highly variable family of isoforms. The isoform CD44v6 has been associated with metastatic spread and poor prognosis in animal models and several human cancers. Results of immunohistological studies in primary colorectal cancer are mostly retrospective and contradictory. The aim of our prospective study was to assess the controversial role of CD44v6 as a prognostic factor in colorectal cancer. METHODS: In 93 patients we analysed tumour CD44v6 expression in prospectively sampled stage I-IV colorectal adenocarcinomas using RT-PCR and Southern blotting. The prognostic value of the CD44v6 expression was assessed using univariate and multivariate analysis. RESULTS: CD44v6 expression was found in 47 % of the cases. CD44v6 expression failed to show any association with the clinical or histological variables examined. CD44v6 expression did not correlate with survival in long-term follow-up. The most important prognostic factor in this cohort was tumour stage. CONCLUSIONS: Changes in CD446 expression level do not predict tumour spread or patient survival in colorectal cancer.

Adenocarcinoma↗

Immunization of healthy adults with a single recombinant pneumococcal surface protein A (PspA) variant stimulates broadly cross-reactive antibodies to heterologous PspA molecules.

Pneumococcal surface protein A (PspA) is a highly variable protein found on all strains of pneumococci. To be successful, a PspA-based vaccine for S. pneumoniae must induce antibodies that are broadly cross-reactive. To address whether cross-reactive antibodies could be induced in man, we evaluated serum from adults immunized with recombinant clade 2 PspA from strain Rx1. Immunization with 5-125 microg rPspA lead to a significant increase in circulating anti-PspA antibodies, as well as antibodies reactive to heterologous rPspA molecules. Increased binding of post-immune sera to 37 pneumococcal strains expressing a variety of PspA and capsule types was observed, versus pre-immune sera. The extent of cross-clade reactivity of human anti-rPspA followed roughly the amount of sequence homology to the non-clade 2 antigens. It is hypothesized that priming of humans by natural exposure to S. pneumoniae contributes to the breadth of the cross-reactivity of antibody to PspA.

Adolescent↗

The potential to use PspA and other pneumococcal proteins to elicit protection against pneumococcal infection.

Pneumococcal proteins, alone, in combination with each other, or in combination with capsular polysaccharide-protein conjugates may be useful pneumococcal vaccine components. Four proteins with a potential for use in vaccines are PspA, pneumolysin, PsaA, and PspC. In a mouse model of carriage, PsaA and PspC were the most efficacious vaccine proteins. Of these, PsaA was the best at eliciting protection against carriage. However, a combination of PspA and pneumolysin may elicit stronger immunity to pulmonary infection and possibly sepsis than either protein alone. Recently, a phase one trial of a recombinant family 1 PspA was completed in man. PspA was observed to be safe and immunogenic. Injection of 0.1 ml of immune serum diluted to 1/400 was able to protect mice from fatal infection with S. pneumoniae. Under these conditions, pre-immune serum was not protective. The immune human serum protected mice from infections with pneumococci expressing either of the major PspA families (1 and 2) and both of the pneumococcal capsular types tested: 3 and 6.

Adult↗

Chondritis attributable to Lactobacillus after ear piercing.

A diabetic patient was admitted with ear pain and purulent discharge after "high ear piercing" by a friend. After investigation she was found to have chondritis, complicated by an abscess. Wound cultures grew Lactobacillus species. Patient responded to parenteral antibiotics without suffering cosmetic deformity. Sterile technique, adherence to post-piercing ear hygiene, and avoiding piercing the auricular cartilage may prevent complications associated with ear piercing. Lactobacillus should be included in the differential of pathogens involved in post-piercing chondritis.

Adolescent↗

Fast magic-angle spinning proton NMR studies of polymers at surfaces and interfaces.

Solid-state proton NMR with fast magic-angle sample spinning has been used to study the structure and dynamics of polymers and the water interface in porous glass composites. The composites were prepared by photopolymerization of poly(ethyl acrylate) and other acrylate formulations in a high surface-area rigid glass matrix with 40-A interconnected pores. High resolution solid-state proton spectra were obtained for polymer films and composites with 15 kHz magic-angle sample spinning at temperatures above the polymer glass transition temperature. The solid-state proton spectra can be detected with high sensitivity and used to determine the composition of polymer and water filling the pores. These results and spin diffusion studies using 1H-29Si 2D heteronuclear correlation and wideline separation NMR show that the polymer fills the central 30 A of the pore, and that the remaining volume is filled with surface hydroxyl groups and water.

Eyeglasses↗

Morphology of tissue damage caused by permanent occlusion of middle cerebral artery in mice.

In two series of experimental occlusion of the middle cerebral artery (MCA) in mice, the time course and the evolution of morphological changes were followed. Both series comprised control animals used in experiments for the screening of neuroprotective and therapeutic effects after focal ischemia. In both series the left MCA was permanently occluded and the animals were sacrificed by perfusion fixation at certain time intervals following occlusion. In the first series the follow up was continued until the 30th day after ischemia. In the second, the observation period was extended to two months. The general question was addressed, whether or not such experimental settings can contribute to the understanding of cellular (necrosis vs apoptosis) and tissue (resorption vs scar) reaction. In the two series the technical procedures were only slightly different. Nevertheless, the development of morphological sequelae was at variance. Differences in tissue reaction in both sets revealed features that were rarely observed in previous protocols. In the first series, infarct areas were different in size, often a central part near the meninges was preserved and gave rise to a prominent mesenchymal reaction. In the second series, infarcts had almost constant size and mesenchymal reaction changes were minimal. The end product in both series, however, was a shallow groove much smaller than the primary well-demarcated defect. We conclude that minor technical variations of MCA occlusion in the mouse demonstrate the variability of occlusion sequelae due to collateral irrigation known from human cerebral pathology. On the cellular level, neuronal death is obviously completed during the first 24 hours in the infarct core. Thus, the mechanism of neuronal damage can only be best observed by morphology at the transition between completed territorial necrosis and unchanged tissue: shrunken neuronal perikarya develop into pycnotic nuclei, that may be interpreted as apoptosis. A second area of partial damage is marked by gliosis. Astrocytic reaction extended far beyond the infarct border, even to the contralateral hemisphere and could represent a component of size compensation.

Animals↗

Clinical impact of ex vivo differentiated myeloid precursors after high-dose chemotherapy and peripheral blood progenitor cell rescue.

The infusion of ex vivo differentiated myeloid precursors may be able to shorten the period of obligatory neutropenia after high-dose chemotherapy and peripheral blood progenitor cell rescue by providing cells capable of differentiating to mature neutrophils within days of infusion. To test this hypothesis, 21 female patients with metastatic breast cancer underwent progenitor cell mobilization with cyclophosphamide, etoposide and G-CSF. CD34+ cells from one to two leukapheresis products were isolated and placed in suspension culture with a serum-free growth medium supplemented with PIXY321. The cultures were maintained for 12 days with subcultures initiated on day 7. The remaining leukapheresis products were cryopreserved in an unmanipulated state. Forty-eight hours after completing high-dose cyclophosphamide, thiotepa and carboplatin, the cryopreserved progenitors were infused, followed 1 to 24 h later by infusion of the differentiated myeloid precursors. In one patient, the cultured cells were labeled with Indium-111 with nuclear imaging performed up to 48 h post infusion. The differentiated myeloid precursors were suitable for infusion in 17 of the patients with a median 13-fold expansion of total nucleated cells. A range of 5.6 to 1066 x 10(7) nucleated cells were infused. Morphologically the cells were predominantly of myeloid lineage (63%) with a median 41% of the cells expressing CD15. No untoward effects were noted with the infusion of the cultured cells. The median days to neutrophil and platelet recovery were 8 and 10 days, respectively. There was a significant relationship (r = 0.67, P = 0.007) between the dose of differentiated myeloid precursors (CD15+ cells) and the depth and duration of neutropenia; a similar relationship, however, was also observed with the dose of cryopreserved CD34+ cells. After infusion of the radiolabeled myeloid precursors, a pattern of distribution similar to radio-labeled granulocytes was noted with uptake detected initially in the lungs and subsequently the reticulo-endothelial system. The impact of differentiated myeloid precursors on neutropenia as an adjunct to high-dose chemotherapy and peripheral blood progenitor cell rescue remains unclear from this study. Further study with controlled doses of cryopreserved progenitors and escalating doses of differentiated myeloid precursors is required.

Adult↗

Teledermatoscopy in Switzerland: a preliminary evaluation.

BACKGROUND: Since devices for digital epiluminescence microscopy and for telemedicine have become affordable, a critical evaluation of this new method has been needed. OBJECTIVE: Our aim was a critical evaluation of teledermatoscopy under routine conditions in private practice. METHODS: Pigmented skin lesions (PSLs) scheduled for excision were documented with a digital epiluminescence microscopy (DELM) system. Images were sent to the PSL consultation at the Department of Dermatology of the University Hospital Geneva, where a diagnosis was established. The histopathologic report including the initial diagnosis was sent afterward. Both approaches were compared concerning diagnostic accuracy. RESULTS: Over a period of 6 months, 55 lesions on 51 patients have been included in this study. Picture quality was good or very good in more than 90%. Diagnostic accuracy of the teledermatoscopy approach was superior to that of the conventional approach for malignant melanocytic lesions. CONCLUSION: We have shown the feasibility of a teledermatoscopic consultation. The gain of diagnostic accuracy in this teledermatoscopic approach, especially for malignant melanocytic lesions, suggests that patients might benefit directly from such a consultation at distance.

Feasibility Studies↗

Use of the selective oral neuraminidase inhibitor oseltamivir to prevent influenza.

BACKGROUND: Safe and effective antiviral agents are needed to prevent infection with influenza A and B virus. Oseltamivir (GS4104), which can be administered orally, is the prodrug of GS4071, a potent and selective inhibitor of influenzavirus neuraminidases. We studied the use of oseltamivir for long-term prophylaxis against influenza in two placebo-controlled, double-blind trials at different U.S. sites during the winter of 1997-1998. METHODS: We randomly assigned 1559 healthy, nonimmunized adults 18 to 65 years old to receive either oral oseltamivir (75 mg given once or twice daily, for a total daily dose of 75 or 150 mg) or placebo for six weeks during a peak period of local influenzavirus activity. The primary end point with respect to efficacy was laboratory-confirmed influenza-like illness (defined as a temperature of at least 37.2 degrees C accompanied by at least one respiratory and at least one systemic symptom). RESULTS: In the two studies combined, the risk of influenza among subjects assigned to either once-daily or twice-daily oseltamivir (1.2 percent and 1.3 percent, respectively) was lower than that among subjects assigned to placebo (4.8 percent; P<0.001 and P=0.001 for the comparison with once-daily and twice-daily oseltamivir, respectively). The protective efficacy of oseltamivir in the two active-treatment groups combined was 74 percent (95 percent confidence interval, 53 to 88 percent) at all the sites combined and 82 percent (95 percent confidence interval, 60 to 93 percent) at sites in Virginia, where the rate of influenza infection was higher than the overall rate. For culture-proved influenza, the rate of protective efficacy in the two oseltamivir groups combined was 87 percent (95 percent confidence interval, 65 to 96 percent). The rate of laboratory-confirmed influenza infection was lower with oseltamivir than with placebo (5.3 percent vs. 10.6 percent, P<0.001). Oseltamivir was well tolerated but was associated with a greater frequency of nausea (12.1 percent and 14.6 percent in the once-daily and twice-daily groups, respectively) and vomiting (2.5 percent and 2.7 percent, respectively) than was placebo (nausea, 7.1 percent; vomiting, 0.8 percent). However, the frequency of premature discontinuation of drug or placebo was similar among the three groups (3.1 to 4.0 percent). CONCLUSIONS: Oseltamivir administered daily for six weeks by the oral route is safe and effective for the prevention of influenza.

Administration, Oral↗

Primary liver disease as a determinant for acute rejection after liver transplantation.

BACKGROUND: Graft rejection and infection remain major problems following liver transplantation; both are heavily influenced by the immunosuppressive regimen. Despite the disparity in the primary disease leading to transplantation, all patients receive the same posttransplant immunosuppressive treatment in a given center. The aim of this study is to detect a possible effect of the underlying disease on the incidence of early acute rejection episodes after orthotopic liver transplantation (OLT). PATIENTS AND METHODS: Retrospective analysis on all 101 consecutive liver transplants performed in 95 patients between 1983 and March 1998; five of these patients, surviving less than 30 days, were not included. The immunosuppressive regimen was based on conventional triple therapy during the whole study period. The diagnosis and treatment of acute rejection within the first 30 days post-OLT was uniform throughout the whole study period. RESULTS: Though there were no differences with respect to patients' characteristics [age, child classification, number of HLA-mismatches or cytomegalovirus (CMV)-serocompatibility], patients with primary biliary cirrhosis (PBC) showed a significant increase of acute rejection after OLT compared with the other patients transplanted for other liver diseases (P = 0.024). The incidence of infection was not elevated in patients transplanted for PBC when compared with other diagnoses. CONCLUSION: Our results indicate that primary liver disease may be a determinant for acute graft rejection in PBC. Furthermore, these results suggest that immunosuppressive regimens based on the underlying disease should be considered.

Acute Disease↗

Determination of acrylic acid in air by using diffusion denuder tubes combined with HPLC technique.

A procedure for the determination of atmospheric acrylic acid in air at the microgram m-3 to mg m-3 level is described. Diffusion-based sampling, designed to discriminate gaseous analytes from their particulate counterparts, has been used. Acrylic acid is collected with an efficiency of > 98% in tubular denuders coated with sodium hydroxide-barium hydroxide-hydroquinone monomethyl ether, and analyzed by high performance liquid chromatography with UV absorbance detection. The detection limit is 2.9 micrograms m-3 at a flow rate of 0.5 L min-1 and 30 min sampling time. A precision (p = 0.95, n = 10) of 7.5% of the overall procedure was achieved at the 100 micrograms m-3 level. Results of laboratory studies concerning the effect of the coating reagent and the relative humidity on the sampling efficiency as well as possible interferences, in particular by ozone, and the elimination of these interferences are discussed. This method was developed to monitor workplace atmospheres as well as ambient air in industrial environments.

Acrylates↗

Non-influenza respiratory viruses may overlap and obscure influenza activity.

OBJECTIVE: To report the number and timing of influenza A isolates, as well as overlapping respiratory viruses. Co-circulating respiratory viruses may obscure the determination of influenza activity. DESIGN: Prospective clinical surveillance for the new onset of respiratory illness followed by viral cultures during seven separate influenza seasons. SETTING: The Wisconsin Veterans Home, a skilled nursing facility for veterans and their spouses. RESULTS: Influenza A isolates were encountered in greater numbers than non-influenza A isolates during three seasons. Seasonal variability is striking. In December 1992, we identified a large outbreak of respiratory illness. Influenza type B was cultured from 102 residents. In December 1995, influenza A was cultured from 285 people in Wisconsin. At that time, we identified outbreaks of respiratory illness in two of our four buildings. Based on statewide data, we suspected an influenza outbreak; however, 26 isolates of parainfluenza virus type 1 were cultured with no influenza. The potential importance of culturing at the end of the season was demonstrated in 1991-1992 when an outbreak of respiratory syncytial virus (RSV) overlapped and extended beyond influenza A activity. CONCLUSIONS: When interpreting new clinical respiratory illnesses as a basis for declaring an outbreak of influenza A, clinicians should realize that co-circulating respiratory viruses can account for clinical illnesses. Clinicians might utilize healthcare dollars efficiently by performing cultures to focus the timing of influenza A chemoprophylaxis. Cultures could be performed when clinical outbreak criteria are approached to confirm an outbreak. Culturing of new respiratory illness could begin again before the anticipated discontinuation of prophylaxis (approximately 2 weeks).

Aged↗

Duration of antiviral prophylaxis during nursing home outbreaks of influenza A: a comparison of 2 protocols.

BACKGROUND: We performed a randomized trial of 2 protocols guiding the duration of antiviral chemoprophylaxis during outbreaks of influenza A in a rural, 700-bed nursing home for veterans and their spouses with 14 nursing units in 4 buildings. METHODS: Half of all residents volunteered to participate. Nursing units were randomized, and the effectiveness of short-term (minimum, 14 days and 7 days without the onset of a case in the building) vs long-term (minimum, 21 days and 7 days without the onset of a case in the 4-building facility) prophylaxis was compared using amantadine hydrochloride in the influenza seasons of 1991-1992 and 1993-1994 and rimantadine hydrochloride in the influenza season of 1994-1995. A "case" is defined as an incident of a respiratory tract illness and the isolation of an influenza virus organism. We compared the number of cases after the discontinuation of short- vs long-term chemoprophylaxis. Prospective surveillance identified residents with new respiratory tract symptoms, and specimens for viral cultures were obtained even in the absence of temperature elevation. RESULTS: We documented influenza A virus activity during 3 seasons (32, 68, and 12 patients, respectively). During the 1991-1992, 1993-1994, and 1994-1995 influenza seasons, the patients on 11 floors were assigned to receive short-term chemoprophylaxis and those on 10 floors were assigned to long-term chemoprophylaxis. Only in 1993-1994 did chemoprophylaxis extend beyond 14 or 21 days when new cases continued beyond 14 days. Amantadine-resistant strains were circulating at that time. None of the participants in the prospective, controlled study had influenza develop after the termination of short- or long-term chemoprophylaxis. CONCLUSION: Antiviral chemoprophylaxis can be administered for the longer duration of 14 days or, in the absence of new culture-confirmed illness in the nursing building, for 7 days.

Aged↗

Activation of the serine proteinase system in chronic kidney rejection.

BACKGROUND: Activation of the serine proteinase system is an important mechanism that contributes to tissue remodeling. In the present study, we analyzed the expression of urokinase plasminogen activator (uPA), urokinase plasminogen activator receptor (uPAR), and plasminogen activator inhibitor type 1 (PAI-1) in samples of chronically rejected human kidneys. METHODS: Using Northern blot analysis, immunohistochemistry, and a uPA activity assay, specimens from 10 chronically rejected kidneys and 10 normal kidney samples were analyzed. RESULTS: By Northern blot analysis, the expression of uPAR and PAI-1 mRNA was 2.9-fold (P<0.05) and 2.3-fold (P<0.05) increased in chronically rejected kidney samples, respectively, compared with normal controls. In contrast, uPA mRNA levels in chronically rejected kidneys were comparable to those in the normal controls. Immunohistochemical analysis in normal kidneys showed weak immunostaining of uPA, moderate to intense uPAR and PAI-1 immunostaining in proximal tubules, and moderate immunostaining in distal tubules, but no signal in the glomeruli or cortical vessels. A similar staining pattern was found in the distal and proximal tubules in rejected kidney tissue samples. However, in the rejected kidneys, the number of tubules was markedly reduced. In addition, within the glomeruli of rejected kidney samples, there was positive immunostaining for uPA, uPAR, and PAI-1 in the mesangial cells, but negative staining in most of the endothelial cells, whereas the normal kidneys revealed no immunoreactivity in these structures. CONCLUSION: The demonstrated up-regulation of uPA/uPAR/PAI-1 in chronic renal rejection is consistent with the plasminogen/plasmin system contributing to tissue remodeling in this disorder. These factors might activate latent transforming growth factor-betas, which have been reported to be enhanced in this disorder, contributing to the generation of the extracellular matrix.

Aged↗

Effect of temperature on hepatic and renal uptake of components from University of Wisconsin solution.

In rat liver and kidney preservation, hepatic and renal uptake of 3H-adenosine, 3H-glutathione, and 3H-raffinose from University of Wisconsin solution and diffusion to the interstitial space were measured. At 4 degrees C only 0.38+/-0.47% and 2+/-0.92% of the total 3H-adenosine remained in the kidney and in the liver, respectively, but at 37 degrees C the amount remaining was 1+/-1% and 12+/-3% (P<0.001). Hepatic and renal uptake of the impermeant 3H-raffinose was unaffected by temperature. During flush out, interstitial accumulation of adenosine was significantly higher in livers than in kidneys and decreased during 24-h cold storage. Glutathione accumulation in the interstitial space was two orders of magnitude lower than 3H-adenosine accumulation and comparable to the impermeant raffinose. In summary, the bioavailability of components of preservation solutions at 4 degrees C is lower than at physiological temperatures, so that the application of cytoprotectants at 37 degrees C to organ donors, rather than simple addition to the cold storage solution, might improve cold storage preservation of livers and kidneys.

Adenosine↗