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Biomedical subjects

M Weiss

Publications and source records attributed to M Weiss.

At least 127 records · Page 7Linked to original sources

Cuniculitrema polymorpha (Tremellales, gen. nov. and sp. nov.), a heterobasidiomycete vectored by bark beetles, which is the teleomorph of Sterigmatosporidium polymorphum.

In a study of the mycobiota associated with bark beetles, a dimorphic fungus producing longitudinally septate basidia of the Tremella-type and yeast cells budding off from stalks, was collected. Detailed morphological, physiological and molecular studies revealed that this fungus represents the teleomorph of Sterigmatosporidium polymorphum. Consequently, a new genus, Cuniculitrema gen. nov., and a new species, C. polymorpha sp. nov., are proposed. Comparative morphological and molecular studies indicated that the new taxon belongs to a group that also comprises species of the stalk-forming anamorphic genera Fellomyces and Kockovaella. The new family Cuniculitremaceae is proposed for this group.

Animals↗

Influence of P-glycoprotein modulators on cardiac uptake, metabolism, and effects of idarubicin.

PURPOSE: The clinical utility of anthracyclines like idarubicin (IDA) is limited by the occurrence of multidrug resistance and cardiotoxicity. Previous studies have demonstrated that the multidrug transporter P-glycoprotein (P-gp) is present in the heart and have suggested that it exerts a protective function. We sought to determine the influence of P-gp inhibitors verapamil and PSC 833 on myocardial uptake, metabolism, and actions of IDA. METHODS: In Langendorff-perfused rat hearts, the outflow concentration-time curve and the residual amount in cardiac tissue of IDA and its active metabolite idarubicinol (IDOL) were measured after 0.5 mg dose of IDA in the absence and presence of the P-gp inhibitors verapamil and PSC 833. RESULTS: During perfusion (80 min), 2% of the IDA dose was converted to IDOL in the heart. Myocardial uptake of IDA was significantly increased by verapamil but not by PSC 833, which increased the recovery of IDA and IDOL. IDA significantly decreased left ventricular developed pressure to approximately 40% and increased coronary vascular resistance to 140% of baseline level, respectively. The vasoconstrictive effect was markedly potentiated by PSC 833. CONCLUSIONS: The enhancement of myocardial IDA uptake by verapamil could be due to a decrease in P-gp-mediated efflux. PSC 833 inhibits cardiac metabolism (non-IDOL pathways) and increases the acute cardiotoxicity of IDA.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Always flush the sampling port before flushing the arterial cannula in pediatric patients.

BACKGROUND: Blood sampling from arterial lines is a frequent event in anesthesia and critical care. To avoid clot formation, both the stopcock outlet and the cannula must be flushed after sampling. We investigated in a bench experiment whether fluid flow through the cannula is affected by the sequence of flushing procedures. METHODS: Continuity of fluid delivery from a vascular cannula was gravimetrically determined using two different flushing techniques with either a syringe pump flush system or a bag flush system. The procedures comprised first flushing the stopcock towards the cannula and then towards the stopcock sampling outlet or the reverse order. Experiments were repeated in triplicate and two sets for each flushing system at hydrostatic pressures of 37 mm Hg and 74 mm Hg. RESULTS: The main finding of the study was that flushing the stopcock towards the outlet after flushing the cannula resulted in considerable retrograde aspiration volumes and zero flow times, in particular in combination with syringe pump flush systems. At a hydrostatic pressure of 74 mm Hg, the observed zero flow time at the cannula tip amounted to (mean+/-SD) 0.1+/-0.01 min with the bag flush system and 7.7+/-0.5 min with the syringe pump flush system. The related retrograde aspiration volumes were 2.2+/-0.7 microl with the bag system and 30.0+/-2.0 microl with the syringe pump system. No backflow was recorded when the stopcock was first flushed to ambient pressure and then afterwards towards the cannula. CONCLUSION: Opening a flush system to ambient pressure affects the continuity of fluid delivery, particularly when using syringe pump flush systems. After blood sampling, the stopcock outlet should be flushed first followed by cannula flushing.

Blood Specimen Collection↗

Comparison of two video-assisted techniques for the difficult intubation.

BACKGROUND: Two recently developed video-optical intubation devices, the video-optical intubation stylet (VOIS) and the angled video intubation laryngoscope (AVIL) were compared for intubation times and success rate in a simulated difficult tracheal intubation setting. METHODS: Thirty anaesthetists were asked to perform 5 intubation attempts with both techniques. Intubation times were recorded and the subjective degree of difficulty and preference for each technique were requested. RESULTS: Intubation time with the VOIS was shorter (17.4+/-6.8 s) than with the AVIL (22.8+/-13.4 s; P=0.0001). Four of the 150 intubation attempts with the AVIL were scored as unsuccessful, due to prolonged intubation time (>60 s). The estimated degree of difficulty was not significantly different. CONCLUSION: In conclusion, both video-assisted intubation devices, the video-optical intubation stylet and the angled video intubation laryngoscope, can be considered to be simple and effective tools which facilitate tracheal intubation and which require only brief instruction and training.

Humans↗

Griscelli syndrome: report of the first peripheral blood stem cell transplant and the role of mutations in the RAB27A gene as an indication for BMT.

Griscelli syndrome is characterized by partial albinism with variable immunodeficiency. Two different gene loci are responsible for this rare, autosomal recessive disease: the myosin Va gene and the RAB27A gene. As recently reported, only patients with mutations of the RAB27A gene suffer from immunodeficiency and hemophagocytic lymphohistiocytosis. Thus, only patients who suffer from the Griscelli syndrome with mutations of the RAB27A gene should receive BMT/PBSCT, which is the only curative therapy. Due to the risk of early relapse or severe infections, BMT/PBSCT should be carried out as soon as possible; if patients do not have HLA-identical family members, valuable time may be lost by searching for an HLA-identical unrelated donor. We report the first peripheral blood stem cell transplant (PBSCT) with T cell depletion in a 6-month-old girl with Griscelli syndrome, and a deletion of the RAB27A gene. The donor was her phenotypically HLA-identical mother. Conditioning included busulfan, VP16 and cyclophosphamide. The patient was transfused with 15.4 x 10(6)CD34-positive cells/kg and 17.6 x 10(3) CD3-positive cells/kg recipient weight. Three months after the transplant, a curable lymphoproliferative syndrome occurred. 26 months after the transplant, the patient is doing well with stable mixed chimerism (52% donor cells).

Bone Marrow Transplantation↗

Secondary acute myelogenous leukemia and myelodysplasia without abnormalities of chromosome 11q23 following treatment of acute leukemia with topoisomerase II-based chemotherapy.

Therapy-related MDS and AML are complications of intensive chemotherapy regimens. Traditionally, patients exposed to topoisomerase II inhibitors are reported to develop secondary AML with abnormalities of chromosome 11q23. We evaluated the long-term hematologic toxicity of topoisomerase II-intensive high-dose mitoxantrone-based chemotherapy in 163 newly diagnosed acute leukemia patients treated over an 8 year period. Nine (5.5%) patients developed new cytogenetic abnormalities. Four patients developed MDS with progression to AML, three patients developed new abnormalities at the time of relapse, and three patients (including one of the former patients) had changes that were not associated with hematologic disease. The abnormalities most frequently involved chromosomes 7q, 20q, 1q, and 13q. Despite the use of topoisomerase II-intensive treatment, no patient developed an abnormality involving chromosome 11q23. Spontaneous resolution of some changes and prolonged persistence of others in the absence of hematologic disease indicates that some cytogenetic changes are not sufficient to promote leukemogenesis.

Acute Disease↗

Cytogenetic and morphological abnormalities in paroxysmal nocturnal haemoglobinuria.

Paroxysmal nocturnal haemoglobinuria (PNH) is characterized by the expansion of a haematopoietic stem cell clone with a PIG-A mutation (the PNH clone) in an environment in which normal stem cells are lost or failing: it has been hypothesized that this abnormal marrow environment provides a relative advantage to the PNH clone. In patients with PNH, generally, the karyotype of bone marrow cells has been reported to be normal, unlike in myelodysplastic syndrome (MDS), another clonal condition in which cytogenetic abnormalities are regarded as diagnostic. In a retrospective review of 46 patients with a PNH clone, we found a karyotypic abnormality in 11 (24%). Upon follow-up, the proportion of cells with abnormal karyotype decreased significantly in seven of these 11 patients. Abnormal morphological bone marrow features reminiscent of MDS were common in PNH, regardless of the karyotype. However, none of our patients developed excess blasts or leukaemia. We conclude that in patients with PNH cytogenetically abnormal clones are not necessarily malignant and may not be predictive of evolution to leukaemia.

Adolescent↗

Use of the intubating laryngeal mask in children: an evaluation using video-endoscopic monitoring.

BACKGROUND AND OBJECTIVE: The intubating laryngeal mask is designed to act as a ventilatory device and as an aid to blind tracheal intubation in adults. The aim of this study was to evaluate the efficacy of the intubating laryngeal mask for ventilation of the lungs and tracheal intubation in children using video-endoscopic control. METHODS: The handling and efficacy of the size 3 intubating laryngeal mask for tracheal intubation in 80 children weighing > or = 25 kg were assessed under video-endoscopic control. Ease of intubating laryngeal mask insertion, adequacy of lung ventilation through the intubating laryngeal mask and airway sealing pressures were recorded. Tracheal intubation was performed blindly by the intubator, while the supervisor observed the procedure on the video display. If blind intubation failed at the first attempt, the monitor view was used to guide the tracheal tube into the trachea. The success rate and time required for successfully placing the tracheal tube were recorded. RESULTS: Insertion of the intubating laryngeal mask was easy in all children. Lung ventilation through the intubating laryngeal mask was uniformly excellent. Blind tracheal intubation at the first attempt was successful in 53 children (66%) within 18.8 +/- 4.1 s. Twenty-four of the 27 failed blind intubation attempts were successfully intubated with video-endoscopic guidance within 28.6 +/- 9.4 s. Two children required replacing the intubating laryngeal mask, one child had to be intubated conventionally. CONCLUSIONS: The size 3 intubating laryngeal mask provides an airway that is easy to establish in children > or = 25 kg with excellent ventilation conditions and allows blind tracheal intubation at the first attempt with a high success rate. Endoscopic monitoring improves its safety and intubation success rate.

Adolescent↗

Teaching and supervising tracheal intubation in paediatric patients using videolaryngoscopy.

In 85 patients (mean age 4.6 +/- 3.1 years, range 0-10 years), a prototype of a new videolaryngoscope was used to provide a display of the intubation procedure in a paediatric anaesthesia teaching unit. The device provided important information to the teacher about the trainee's problems related to direct laryngoscopy, difficulties with tube insertion into the larynx as well as the need and extent for anterior laryngeal pressure. Because the videolaryngoscope did not impair the normal intubation procedure, it seems to be a safe and a benefical tool for teaching and supervising tracheal intubation in children. In addition, it provides a potentially useful aid during difficult laryngoscopy, since the monitor view of the vocal cords was significantly better compared with a direct laryngoscopic view (P < 0.001).

Audiovisual Aids↗

Start-up delays of infusion syringe pumps.

BACKGROUND: We performed a bench experiment to investigate the extent of start-up delays in fluid delivery for four different syringe pumps after initially placing the infusion syringe in the syringe pump. METHODS: Pump performance was determined at an infusion rate of 1 ml.h-1 with and without a fluid bolus delivered by the infusion pump prior to connecting the infusion line to the simulated patient. RESULTS: The time (mean +/- SD) from starting the pump up to first fluid delivery (t1) differed considerably between pumps (from 6.75 +/- 4.4 to 57.2 +/- 28.6 min) as did the time to steady state fluid delivery (t2) (from 19.6 +/- 9.3 to 76.3 +/- 29.0 min). Applying an initial bolus of 2 ml before connecting the line to the simulated patient practically eliminated the delay in fluid delivery (t1 ranging from 0.3 +/- 0.1 to 1.1 +/- 0.8 min). This manoeuvre also reduced the time to steady flow delivery (t2 from 6.0 +/- 3.1 to 11.1 +/- 4.3 min, P<0.001) and minimized the differences between syringe pumps. CONCLUSIONS: Syringe pump design affects start-up delay times because of free play of the syringe. These delays can be eliminated by a start-up bolus of 2 ml prior to connecting the infusion line to the patient.

Equipment Design↗

[Concentrations of diclofenac in aqueous humor and in plasma after i.v. injection in 59 patients undergoing cataract surgery--a prospective study].

BACKGROUND: The mean diclofenac level in the aqueous humor after i.v.-injection should be examined as an example for other systemic applied drugs. The clinical effect is to be evaluated with regard to perioperative anti-inflammatory therapy in patients undergoing cataract surgery. PATIENTS AND METHODS: In this prospective clinical study 59 patients (age 41-86 years) scheduled for phacoemulsification by the tunnel technique, received 75 mg diclofenac-sodium by short time i.v.-infusion (30 min) within an interval between 30 min and 7 h before surgery. Aqueous humor samples and one blood sample were taken at the beginning, and a second blood sample was taken at different time intervals before surgery. RESULTS: The plasma concentration of diclofenac one minute after infusion was 13,961 +/- 4277 ng/ml. The concentration decreased rapidly during the distribution phase (1305 +/- 324 ng/ml after 40 min) and reached after 336 min 419 +/- 277 ng/ml. A concentration of 83.9 ng/ml diclofenac was found for the last sampling point after 353 min in the elimination phase. The mean diclofenac concentration in the aqueous humor reached after about 60 min the highest level (21.7 +/- 12.7 ng/ml). This level decreases to 4.4 +/- 0.4 ng/ml (120 min) and 3.1 +/- 1.3 ng/ml (300 min), respectively. CONCLUSIONS: The calculated mean residence time of diclofenac molecules in aqueous humor of 123 min matched the mean disposition residence time of diclofenac in the body (119 min).

Adult↗

[Antiinfectious prophylaxis in asplenia].

Asplenia in childhood may be congenital (e.g. Ivemark-syndrome) or acquired (functional hyposplenism in sickle cell disease; after splenectomy or bone marrow transplantation). Hereditary spherocytosis is the most common indication for splenectomy in childhood. Virtually every patient without spleen has a significantly increased risk of severe postsplenectomy infection (mostly caused by Streptococcus pneumoniae). Therefore, vaccinations against pneumococci, haemophilus influenzae and, under certain circumstances, meningococci are recommended. In addition a continuous prophylaxis with antibiotics should be performed for at least three years (or even longer depending on the disease) after splenectomy followed by lifelong interventional application of broad spectrum antibiotics in case of any unclear infection or high fever. This prophylaxis must be started as early as four months of age in sickle cell disease. In future the use of penicillin may be hampered by the growing resistance of pneumococci. Due to this fact the indication for splenectomy in childhood should be restricted to patients with hematologic disease (spherocytosis and other hemolytic anemias, chronic ITP etc.) and moderate to severe symptoms. It is unclear whether partial splenectomy for spherocytosis (and other hemolytic anemias) is an alternative regarding both longlasting reduction of hemolysis and prevention of severe infection. After trauma every effort should be undertaken to preserve a splenic remnant.

Age Factors↗

Hypertonic-hyperoncotic solutions decrease cardiac troponin I concentrations in peripheral blood in a porcine ischemia-reperfusion model.

In this study we addressed the question of whether the measurement of cardiac Troponin I (cTnI) is able to reflect beneficial effects of hypertonic-hyperoncotic solutions after transient cardiac arrest. Ten pigs were anaesthetized and cardiac arrest was induced by electric fibrillation. After 5 minutes of global ischemia, cardiac arrest was reversed by electric defibrillation. Upon return of spontaneous circulation 5 animals received hypertonic-hyperoncotic solutions (10% Hydroxyethylstarch 200/0.5 and 7.2% NaCl). The other animals received equivalent volumes of physiological saline. We observed that cTnI serum levels of animals treated with hypertonic-hyperoncotic solutions were significantly lower than those treated with saline. We conclude that hypertonic-hyperoncotic solutions may have cardioprotective effects.

Animals↗

Xenotransplantation of bovine bone marrow stromal cells into pig fetuses: incorporation into skeletal muscle.

Bone marrow stromal cells are multipotent and have been shown to differentiate into a wide variety of mesenchymal cell types in vivo. In this study we tested the ability of bovine bone marrow stromal cells to contribute to the development of porcine skeletal muscle tissue. Fetal pigs were injected early in gestation with bone marrow stem cells originating from slaughtered steers. After approximately forty days of development the fetuses were harvested and sections of their skeletal muscle were analyzed for the presence of bovine cells. PCR was used to detect bovine DNA present in DNA extracted from the fetal pig skeletal muscle. We also used a PRINS (Oligonucleotide Primed In- Situ Synthesis) protocol to confirm the presence of bovine cells within the porcine skeletal muscle tissue sections. The results of both assays indicate that bovine bone marrow stromal cells can participate in the development of porcine skeletal muscle. This study helps to demonstrate the potential that bone marrow stromal cells have to contribute to advances in animal biotechnology and medicine.

Animals↗

Use of angulated video-intubation laryngoscope in children undergoing manual in-line neck stabilization.

Laryngeal views obtained during direct laryngoscopy with and without manual in-line neck stabilization (MILNS) and during video-assisted intubation with MILNS using the angulated video-intubation laryngoscope were assessed in 100 paediatric patients (aged 0.25-17.3 yr). Visualization of the larynx (Cormack and Lehane score) as well as time taken for video-assisted tracheal intubation by six nurses and four resident anaesthetists not experienced in the technique were recorded. Cormack and Lehane scores were significantly worse during direct laryngoscopy when MILNS was applied. Video-assisted visualization of the larynx during MILNS produced scores, which were as good or better than those observed during direct laryngoscopy alone. Intubation times ranged from 19-75 s (mean 35 (SD 13.4); median 32).

Adolescent↗

Growth inhibition and induction of apoptosis in colorectal tumor cells by cyclooxygenase inhibitors.

Non-steroidal anti-inflammatory drugs (NSAIDs) inhibit colorectal carcinogenesis and prevent or revert the growth of premalignant colonic polyps. They inhibit cyclooxygenase (COX) but recent data indicate that this is not the only or even the most important mechanism of inhibition in colorectal tumor cells. We have used colonic carcinoma and adenoma cell lines to study the effects of the NSAID sulindac sulfide, its COX-inactive metabolite, sulindac sulfone, and the isoenzyme-specific inhibitors SC58125, SC236 and SC58560 on tumor cell growth in relation to COX-2 expression and prostaglandin production. To establish the role of COX-2 in NSAID action, we constructed clones expressing different levels of COX-2 from SW480 cells. All five compounds inhibited DNA synthesis and/or induced apoptosis, each with a characteristic pattern. ID(50)s were very similar in all the cell lines and were independent of COX expression, except for the COX-1 inhibitor SC58560, which was least effective in HT29/HI1, the cell line expressing the highest level of COX-1 (ID(50) 70 microM; in other cells lines the ID(50) was 15 microM). For all other compounds ID(50) concentrations varied less than two-fold: 25-40, 40-90 and 150 microM for SC236, sulindac sulfide and sulindac sulfone, respectively. SC58125 was the weakest inhibitor, never causing >50% cell loss. All compounds modulated expression of Bcl-2 and Bak and activated caspase 3. Overexpression of COX-2 in SW480 cells protected them against induction of apoptosis by sulindac sulfide. The effect was restricted to clones producing high levels of prostaglandin E(2). In summary, our data indicate that both COX-dependent and COX-independent mechanisms are involved in NSAID-induced growth in colorectal tumor cells. The concentrations necessary to inhibit growth were higher than serum concentrations that can be obtained in vivo, indicating that the therapeutic effect of NSAIDs cannot be explained by a direct effect of NSAIDs on the epithelial cells alone. For therapeutic purposes, compounds using different targets could be used to minimize side effects while optimizing therapeutic effect.

Adenoma↗

Anaesthetics and immune function.

Surgical trauma and anaesthetics may cause immune suppression, predisposing patients to postoperative infections. Furthermore, stress such as surgery and pain per se is associated with immune suppression which, in animal models, leads to an increased susceptibility to infection and tumour spread. Thus, by modulating the neurohumoral stress response, anaesthesia may indirectly affect the immune system of surgical patients. In particular, regional anaesthesia attenuates this stress response and the associated effects on cellular and humoral immunity. Additionally, anaesthetics may directly affect the functions of immune-competent cells. However, the reported effects of commercial preparations of, for example, propofol, etomidate and midazolam are highly dependent on the applied solvent. Immunosuppressive effects may be particularly relevant in the intensive care unit when anaesthetics are used as long-term sedatives. There is a striking body of evidence that long-term exposure to certain sedatives is paralleled by infectious complications. On the other hand, anti-inflammatory effects of anaesthetics may be therapeutically beneficial in distinct situations such as those involving ischaemia/reperfusion injury or the systemic inflammatory response syndrome. Consequently, sedatives should be administered with careful regard to their respective potential immunomodulatory properties, the clinical situation, and the immunity status of the critically ill patient.

Journal Article↗