Technical note: Effects of frozen storage on the mechanical properties of the suspensory tissue in the bovine claw.

It is proposed that a softening of the suspensory tissue in the claw is involved in the development of lameness and claw lesions in cattle. A relatively small amount of research has been carried out to verify this theory. Research in this area would be simplified if mechanical testing of the suspensory tissue could be performed on frozen and stored specimens. The current study tested whether freezing of the specimens changes the suspensory tissues' mechanical properties. Limbs from 3 freshly slaughtered Danish Holstein dairy cows and 6 nonpregnant Angus heifers, without clinical signs of lameness, were allocated to 1 of 2 treatments (frozen or nonfrozen) in such a way that each cow was represented in each treatment group with a frozen limb and a corresponding nonfrozen limb (i.e., frozen left front, fresh right front, and so on). The frozen limbs were kept at -18°C for a week before processing and the nonfrozen limbs were processed within 2h of slaughter. Two samples measuring 8 × 8 mm were cut from the abaxial side of each claw in such a way that the sample included the horn of the abaxial wall, pedal bone, and the interposed corium. The samples were kept on ice until being mounted in a large deformation rheometer with an extension testing frame, fixed by the horn and the pedal bone, and loaded to failure. During deformation force and displacement data were recorded, from which corresponding stress and strain were calculated. Young's modulus (a measure of tissue elasticity or stiffness) and a measure of physiological support (PS; force needed to displace the sample 1mm) were calculated from the data. The response variables, Young's modulus and PS, were analyzed separately by a mixed model. The explanatory variables were treatment (frozen or nonfrozen), limb (front or back), claw (medial or lateral), position of the sample (dorsal or palmar-plantar), and group (Angus or Holstein). Interactions between group and treatment and between limb, claw, and sample position were included in the model. Cow identity was included as a random effect. Model reduction was performed by stepwise backward elimination, until all remaining terms were significant at the 5% level or less. Freezing had no effect on the elasticity of the suspensory apparatus or on PS. However, PS was affected by limb (hind legs had higher PS values than front) and the position of the sample (palmar-plantar samples had higher PS values than dorsal). The Angus group had higher PS values than the Holstein group, but the groups differed in age, parity, body weight, lactation, housing, and management, as well as in breed; therefore, further studies are needed to investigate these effects. The results indicate that mechanical testing of bovine claw suspensory tissue can be performed on specimens that have been frozen, thus aiding research in the mechanical aspect of bovine lameness and claw lesions.

Chemoradiotherapy with concurrent gemcitabine and cisplatin with or without sequential chemotherapy with gemcitabine/cisplatin vs chemoradiotherapy with concurrent 5-fluorouracil in patients with locally advanced pancreatic cancer--a multi-centre randomised phase II study.

BACKGROUND: No standard treatment for locally advanced pancreatic cancer (LAPC) is defined. PATIENTS AND METHODS: Within a multi-centre, randomised phase II trial, 95 patients with LAPC were assigned to three different chemoradiotherapy (CRT) regimens: patients received conventionally fractionated radiotherapy of 50 Gy and were randomised to concurrent 5-fluorouracil (350 mg m(-2) per day on each day of radiotherapy, RT-5-FU arm), concurrent gemcitabine (300 mg m(-2)), and cisplatin (30 mg m(-2)) on days 1, 8, 22, and 29 (RT-GC arm), or the same concurrent treatment followed by sequential full-dose gemcitabine (1000 mg m(-2)) and cisplatin (50 mg m(-2)) every 2 weeks (RT-GC+GC arm). Primary end point was the overall survival (OS) rate after 9 months. RESULTS: The 9-month OS rate was 58% in the RT-5-FU arm, 52% in the RT-GC arm, and 45% in the RT-GC+GC arm. Corresponding median survival times were 9.6, 9.3, and 7.3 months (P=0.61) respectively. The intent-to-treat response rate was 19, 22, and 13% respectively. Median progression-free survival was estimated with 4.0, 5.6, and 6.0 months (P=0.21). Grade 3/4 haematological toxicities were more frequent in the two GC-containing arms, no grade 3/4 febrile neutropaenia was observed. CONCLUSION: None of the three CRT regimens tested met the investigators' definition for efficacy; the median OS was similar to those previously reported with gemcitabine alone in LAPC.

[Severe accidental hypothermia with cardiac arrest and extracorporeal rewarming. A case report of a 2-year-old child]. / Schwere akzidentelle Hypothermie mit Kreislaufstillstand und extrakorporaler Erwärmung. Fallbericht eines 2-jährigen Kindes.

In patients with severe hypothermia and cardiac arrest, active rewarming is recommended by extracorporeal circulation with cardiopulmonary bypass. The current guidelines for resuscitation of the European Resuscitation Council now include the recommendation regarding patients with hypothermia remaining comatose after initial resuscitation to accomplish an active rewarming only up to a temperature of 32-34 degrees C and to maintain a mild hypothermia for 12-24 h. We report the case of a 2-year-old boy who suffered from severe hypothermia after falling into ice-cold water. On discovery cardiac arrest with asystole was present and the first measured temperature was 23.8 degrees C. Resuscitation led to restoration of spontaneous circulation. The patient was rewarmed by extracorporeal circulation with cardiopulmonary bypass to 33 degrees C then mild hypothermia was maintained for a further 12 h. On the third day after the accident the patient was extubated and after a further 9 days was discharged without any sequelae.

Sevoflurane anaesthesia does not induce the formation of sister chromatid exchanges in peripheral blood lymphocytes of children.

BACKGROUND: Compound A, a degradation product of sevoflurane, has been demonstrated to induce sister chromatid exchanges (SCE) in Chinese hamster ovary cells in vitro as a marker for possible genotoxicity. We investigated the formation of SCE in mitogen-stimulated T-lymphocytes of 40 children undergoing sevoflurane anaesthesia for minor surgical procedures. METHODS: Anaesthesia was induced by inhalation of up to 8% sevoflurane and maintained at 2.5-3% in oxygen/nitrous oxide (65/35%) at a fresh gas flow of 3 litre min(-1). Soda lime (humidity 12-15%) was used as a carbon dioxide absorbent. Blood was drawn directly before induction and after termination of anaesthesia. Twenty-five second division metaphases of mitogen-stimulated T-lymphocytes per blood sample were screened for SCE rates using standard techniques. RESULTS: Average duration of anaesthesia was 49.6 (SD 24.0) min. Before anaesthesia induction, 7.93 (1.23) SCE per metaphase were determined. After sevoflurane anaesthesia [1.40 (0.77) MAC h] 7.92 (1.19) SCE per metaphase were observed. Additionally, no differences were evident between male or female children. CONCLUSION: Short-term administration of sevoflurane anaesthesia did not induce SCE in T-lymphocytes of children. No indication for a possible genotoxic effect has been observed.

Value of XML in the implementation of clinical practice guidelines--the issue of content retrieval and presentation.

The purpose of guidelines in clinical practice is to improve the effectiveness and efficiency of clinical care. It is known that nationally or internationally produced guidelines which, in particular, do not involve medical processes at the time of consultation, do not take local factors into account, and have no consistent implementation strategy, have limited impact in changing either the behaviour of physicians, or patterns of care. The literature provides evidence for the effectiveness of computerization of CPGs for increasing compliance and improving patient outcomes. Probably the most effective concepts are knowledge-based functions for decision support or monitoring that are integrated in clinical information systems. This approach is mostly restricted by the effort required for development and maintenance of the information systems and the limited number of implemented medical rules. Most of the guidelines are text-based, and are primarily published in medical journals and posted on the internet. However, internet-published guidelines have little impact on the behaviour of physicians. It can be difficult and time-consuming to browse the internet to find (a) the correct guidelines to an existing diagnosis and (b) and adequate recommendation for a specific clinical problem. Our objective is to provide a web-based guideline service that takes as input clinical data on a particular patient and returns as output a customizable set of recommendations regarding diagnosis and treatment. Information in healthcare is to a very large extent transmitted and stored as unstructured or slightly structured text such as discharge letters, reports, forms, etc. The same applies for facilities containing medical information resources for clinical purposes and research such as text books, articles, guidelines, etc. Physicians are used to obtaining information from text-based sources. Since most guidelines are text-based, it would be practical to use a document-based solution that preserves the original cohesiveness. The lack of structure limits the automatic identification and extraction of the information contained in these resources. For this reason, we have chosen a document-based approach using eXtensible Markup Language (XML) with its schema definition and related technologies. XML empowers the applications for in-context searching. In addition it allows the same content to be represented in different ways. Our XML reference clinical data model for guidelines has been realized with the XML schema definition. The schema is used for structuring new text-based guidelines and updating existing documents. It is also used to establish search strategies on the document base. We hypothesize that enabling the physicians to query the available CPGs easily, and to get access to selected and specific information at the point of care will foster increased use. Based on current evidence we are confident that it will have substantial impact on the care provided, and will improve health outcomes.

Presentation of problem-specific, text-based medical knowledge: XML and related technologies.

Systematic reviews of the impact of clinical decision support systems on provider behavior and patient outcome have shown evidence of benefit. Knowledge-based functions for decision support or monitoring that are integrated in clinical information systems are a potentially effective way. But these concepts are restricted by the efforts required for development and maintenance of the information systems and the limited number of implemented medical rules. Physicians are familiar to get their information from text-based sources. It seems to be straight-forward to rely on a document-based solution in order to present problem-specific information at the point of care. We have developed a concept for context-sensitive retrieving and presentation of text-based medical knowledge (textbook of internal medicine) using the eXtensible Markup Language (XML) and related technologies. This concept can facilitate the electronic query and presentation of this resource. XML may replace narrative text as a storage format and allows to structure the data in a stepwise fashion. On the basis of structured data we are able to improve the search quality for clinical information and its presentation which forms a crucial pre-requisite for the use of the information and the implementation of evidence-based care in the clinical routine.

Topical amphotericin B application in severe bronchial aspergillosis after lung transplantation: report of experiences in 3 cases.

Ulcerative tracheobronchial aspergillosis after lung transplantation (ltx) may lead to bronchial-pulmonary artery fistula that results in fatal bleeding. We report our early experience with combined systemic, aerolized and topical application of amphotericin B in 3 cases of bronchial aspergillosis after ltx. Two patients are still alive, but 1 died of bleeding from a fistula between the left upper lobe bronchus and the pulmonary artery. Aspergillosis in the second patient resolved with minimal stenosis of the left main and the left upper lobe bronchus, and the third patient developed an anastomotic stenosis that was successfully dilated.

Value of a multileaf prescription preparation system for palliative external beam irradiation.

In palliative treatment, irregularly shaped fields are used to reduce side-effects and can improve, or avoid, field matching. We investigated the effectiveness of a multileaf collimator (MLC) supported by a digitizing data entry system in the palliative radiotherapy treatment of 66 patients and compared it with conventional shielding with geometrically shaped blocks. After conventional simulation of rectangular fields, irregular field shapes were marked on the simulator film in 17 patients (27%) to reduce radiotherapy related side-effects. Individual leading was performed with an MLC. Digitizing and fitting of the optimum leaf position were carried out using a multileaf preparation system (MLP, Elekta, Crawley, UK). Target volumes included bone metastases in the pelvis, spine and extremities, mediastinal soft tissues, lymph nodes and central nervous system. In 10 patients, treated with a parallel pair for pelvic metastases, MLC and conventional shielding were prospectively compared with regard to time requirements and area shielded. Compared with conventional blocking, the mean simulation, preparation and treatment time required for MLP fields was shorter (9.55 +/- 1.44 min vs 16.90 +/- 2.64 min, and 5.50 +/- 1.14 min vs 8.97 +/- 1.75 min). The mean shielded area was 31 cm2 larger for MLC fields compared with geometrically shaped blocks (p < 0.05). Compared with cerrobend blocking, the use of an MLC, supported by preparation data entry software, is more flexible and reduces radiotherapy resources. Therefore, a preparation data entry system as a separate device, or integrated into the treatment planning system, is a useful tool in palliative treatment.

Povidone-iodine to prevent mucositis in patients during antineoplastic radiochemotherapy.

In an open study, the efficacy of povidone-iodine in the prophylaxis of mucositis during antineoplastic radiochemotherapy was determined. 40 patients were randomly assigned to a treatment or control group (each 20 patients). All patients received standard prophylaxis of mucositis with nystatin, dexpanthenol, rutoside and immunoglobulin. In addition, the patients of the treatment group performed 4 times daily rinsing with povidone-iodine, the control patients with sterile water. Clinical examination of the oral mucosa was performed weekly during the radiation period and up to 6 weeks after the end of therapy. Oral mucositis was observed in 14 patients of the treatment group (mean grading: 1.0) and in all 20 patients of the control group (mean grading: 3.0). The mean onset of mucositis was after 2.25 weeks in treatment patients and 1.5 weeks in control patients. The mean total duration of mucositis was 2.75 weeks in treatment patients and 9.25 weeks in control patients. The mean AUC values were 2.5 in treatment patients and 15.75 in control patients. All findings were statistically significantly different between the two groups. It is concluded that rinsing with povidone-iodine reduces the incidence, severity and duration of oral mucositis during antineoplastic radiochemotherapy.

Comparison of two strategies for the treatment of radiogenic leukopenia using granulocyte colony stimulating factor.

PURPOSE: Radiation-induced leukopenia can cause a delay or discontinuation of radiotherapy. This complication can be overcome with the use of granulocyte colony-stimulating factor (G-CSF). However, an uncertainty exists regarding the mode of application of G-CSF in patients treated with radiotherapy. For this reason, the efficacy of two strategies for the administration of G-CSF in irradiated patients was compared in a prospective randomized clinical study. METHODS AND MATERIALS: Forty-one patients who developed leukopenia (< 2.5 x 10(9) per liter) while undergoing radiotherapy were treated with G-CSF at a daily dose of 5 microg/kg. The first group received single injections of G-CSF as required (n = 21). The second group received G-CSF on at least 3 consecutive days (n = 20). An analysis was made of the changes in leukocyte counts, the number of days on which radiotherapy had to be interrupted, and the side effects of growth-factor treatment. RESULTS: An increase in leukocyte values in the peripheral blood was observed in all patients treated with G-CSF. In the group which received G-CSF when required, two injections (range: 1-8) were administered in most cases. In the second group, most of the patients received three injections (range: 3-9). The average duration of therapy interruptions due to leukopenia was 4.8 days (0-28) in the first therapy arm and 2.5 (0-20) in the second arm. The variance in the duration of therapy interruptions between the two groups was not significant (p = 0.2). Radiotherapy had to be terminated in two patients due to thrombocytopenia but the application of G-CSF did not seem to be a reason of decreasing platelet counts. CONCLUSIONS: Our results reveal that G-CSF is safe and effective in the treatment of radiation-induced leukopenia regardless of the mode of application. Because the calculated difference related to radiation treatment interruptions has no clinical relevance, both approaches examined in our study appear reasonable.

Localization of lysosomal acid phosphatase mRNA in mouse tissues.

We studied the expression of lysosomal acid phosphatase (LAP) in mouse by hybridizing Northern blots and tissue sections with the mouse LAP cDNA. Three mRNA species of 2.3, 3.2 and 5.2 KB were identified, which differ in the length of their 3' untranslated region (UTR). The 3.2 KB mRNA is expressed in equal amounts in all tissues and represents the major species in most tissues, whereas the amounts of the 2.3 and 5.2 KB species differ. In situ hybridization of different tissues of adult mice showed a uniform expression of LAP, as expected for a housekeeping gene, except in testis and brain. In testis we found an increase in the LAP mRNA level in spermatocytes. By Northern blot analysis of young mouse testis, this increase could be attributed to late pachytene primary spermatocytes or secondary spermatocytes. In brain tissue the neurons were predominantly labeled, especially the Purkinje and pyramidal cells, whereas glial cells expressed only low amounts of LAP mRNA. Very high LAP expression was also found in the epithelial cells of the choroid plexus. Analysis of LAP expression during mouse embryonic development between Days 9.5 and 17.5 revealed a prominent expression relative to other tissues in the neural tube from Day 9.5 to Day 13.5.