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Biomedical subjects

A Linder

Publications and source records attributed to A Linder.

At least 19 recordsLinked to original sources

Mortality in Swedish dairy calves and replacement heifers.

The mortality of 8,964 heifer calves born in 122 dairy herds in southwest Sweden in 1998 to 2000 was monitored from January 1998 until December 2000. Farmers were requested to send carcasses for necropsy from animals that died from 1 d of age to first calving. Age and seasonal patterns of mortality were investigated using Kaplan-Meier curves. The median herd-level mortality risk was 2.1%. In total, 3.1% of the animals died before 90 d of age, 0.9% between d 91 and 210, and 2.2% between d 211 and first calving or d 810 (27 mo of age). The median age at death was 50 d and the risk of dying was highest during the first week of life. Of the 421 dead animals, 236 (56%) were subjected to either postmortem examination or were diagnosed as having died from trauma based on information from the farmers. In total, pneumonia was the most common cause of death (27%). However, in calves less than 31 d old, enteritis was the most common cause of death; in young stock 211 to 450 d old, trauma dominated; and in young stock more than 450 d old, trauma and calving-related diseases accounted for a majority of the mortality. The largest proportion of deaths was observed from January to March, and in June. Kaplan-Meier curves suggested that housing in small-group pens was associated with the lowest mortality (other housing systems were single pens and large-group pens with automatic milk feeders), but the association was not significant.

Age Factors↗

Melanoma associated antigen (MAGE)-A3 expression in Stages I and II non-small cell lung cancer: results of a multi-center study.

OBJECTIVES: Adjuvant immunotherapy is an innovative therapeutic option that might potentially improve outcome of early-stage non-small cell lung cancer. Melanoma associated antigen (MAGE)-A3 is a promising target for immunotherapy because it is exclusively presented on the cell surface of cancer cells and might be associated with an aggressive cancer phenotype. The present study was performed to determine the rate of MAGE-A3 expression in early-stage non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Primary tumor samples from 204 patients with operable clinical Stages I or II NSCLC were collected between March and November 2001. Pathological Stage was determined by the local pathologist in each of the 16 participating institutions. Tissue samples were stored immediately after surgery in a RNA-stabilizing solution and were frozen at -20 degrees C. MAGE-A3 expression was analyzed by detection of MAGE-A3 transcripts using reverse-transcriptase polymerase chain reaction. RESULTS: MAGE-A3 expression was observed in 80 out of the 204 (39.2%) examined Stages I-II primary tumors. Stratification into UICC-Stages showed that 31 out of 105 (29.5%) Stage I non-small cell lung cancers and 49 out of 99 (49.5%) Stage II non-small cell lung cancers expressed MAGE-A3. In comparison to Stage I, the rate of MAGE-A3 positive tumors was significantly increased in Stage II (P=0.004; Chi-square test). CONCLUSION: The MAGE-A3 expression rate showed that a promising proportion of operable patients with early-stage non-small cell lung cancers are possible candidates for trials investigating adjuvant therapy with MAGE-A3 immunization. Currently, a phase two trial of adjuvant MAGE-A3 vaccination is in progress.

Antigens, Neoplasm↗

Postweaning multisystemic wasting syndrome--PMWS. the first year with the disease in Sweden.

Postweaning multisystemic wasting syndrome (PMWS) is causally associated with porcine circovirus type 2 (PCV2) infection of pigs. PCV2 has been present in the Swedish pig population for at least ten years. Despite this, no signs of PMWS were observed in pigs of Sweden until 2003. Since then the disease has spread slowly in Sweden. The pig population of Sweden is geographically isolated, the density of pigs and the pathogen load in the country is low and the trade of animals is organised in a restricted way. To date, there has been little information placed in the peer-reviewed literature on the study of the spread of PMWS in a country during the early phase of the disease outbreak, mainly because diagnosis of PMWS has only occurred after the disease has been recognised on a number of farms. This manuscript documents the studies to date on the PMWS outbreak in Sweden which has been closely monitored since the initial outbreak of diseases on a single farm in 2003 was diagnosed. In Sweden PMWS was officially reported for the first time at a progeny test station during December 2003. One year later sixteen herds have been diagnosed and reported to the authorities: one progeny test station, one nucleus herd, thirteen piglet producers or integrated herds and one specialised fattening herd. Fifteen suspected cases have been deemed negative for PMWS with disease scenarios associated with Lawsonia intracellularis, Brachyspira pilosicoli, Mycoplasma hyopneumoniae, shortcomings in feed composition etc. To date, one year after the index case was reported ten other herds suspected for PMWS are under observation. The PMWS cases are concentrated into the southern part of Sweden. However, the disease is spreading slowly, and in general there are no obvious physical links between affected herds. The data generated to date in Sweden suggest that introduction of a new contagious microbe into the country that is responsible for the PMWS outbreaks appears unlikely, as does the spread of PMWS via semen.

Animals↗

Dynamic performances of different seat designs for low to medium velocity rear impact.

There is good evidence that seat design and impact severities in terms of delta-V and acceleration plays a role in AIS 1 neck injury outcomes in the event of a rear impact. This study evaluates a number of current production seats to assess the AIS 1 neck injury protection potential at different impact severities. Five different seat designs were exposed to four different impact severities in a sled simulating a rear impact. The same delta-V produced with different peak accelerations generated very different dummy responses. Head restraint position influenced the angular and horizontal displacement of the head relative to torso and the time of head to head restraint contact. The lowest motion of the head relative to the torso was found in the two anti-whiplash seats tested. The results of the study can be used for the design of future vehicle seats and anti-whiplash systems.

Abbreviated Injury Scale↗

Variability of cyclophosphamide uptake into human bronchial carcinoma: consequences for local bioactivation.

PURPOSE: The alkylating cytostatic prodrug cyclophosphamide is bioactivated by the human cytochrome P450 enzyme system. Since these enzymes are not only expressed in human liver, but also in extrahepatic tissue, local bioactivation of this drug may play an important role in its antineoplastic effects, e.g., chemotherapy of lung tumors. This would require uptake of significant amounts of cyclophosphamide into tumor tissue, which has not yet been demonstrated. METHODS: We used a recently developed, ex vivo isolated, ventilated and perfused human lung model to study cyclophosphamide uptake into bronchial carcinoma and healthy lung tissue. Following a standard lobectomy, lung samples containing the tumor were perfused with buffer containing 2 mM cyclophosphamide for 2 h. Cyclophosphamide concentrations in perfusate and healthy peripheral tissue were measured during the perfusion and in tumors at the end of perfusion. RESULTS: In all tissue samples, cyclophosphamide uptake was relatively poor, indicated by a tissue to perfusate ratio of 0.021. Moreover, in tumor samples, cyclophosphamide concentrations were significantly lower (P < 0.05) than in healthy lung tissue and showed pronounced interindividual variability. Median concentrations were 36.8 microg/g (26.9 44.2 microg/g) in healthy tissue and 5.1 microg/g (0.0-26.8 microg/g) in tumor samples. Tumor cyclophosphamide concentrations varied between 0 and 75% of those reached in healthy tissue. CONCLUSIONS: Our results indicate that CP tumor concentrations are modulated by factors different from dose and that expression of bioactivating enzymes in human lung or transfection of genes encoding these enzymes into tumor cells does not necessarily lead to local bioactivation of cyclophosphamide.

Aged↗

The validity of telepathological frozen section diagnosis with ISDN-mediated remote microscopy.

We investigated 109 randomly selected frozen section specimens from lung surgery patients in a retrospective blind mode using telepathology equipment. The telepathology system applied (HISTKOM) used one ISDN B-channel and telemicroscopy with a remotely operated robotic microscope. The performance of telepathological frozen section diagnosis was compared with that of conventional frozen section diagnosis. The false-positive rate achieved was identical for both methods. The sensitivity (P=0.03), but not the specificity, was significantly lower for the telepathological method. The time needed to establish a diagnosis with the remote microscope was too high; therefore, upgrading to multichannel technology is recommended. The quality of the images transmitted was judged to be sufficient by the pathologists involved in the study. In conclusion, with further technical improvements in telemicroscopy and additional experience in telepathology, remote diagnosis seems to be feasible.

Adult↗

A new mathematical neck model for a low-velocity rear-end impact dummy: evaluation of components influencing head kinematics.

A mathematical model of a new rear-end impact dummy neck was implemented using MADYMO. The main goal was to design a model with a human-like response of the first extension motion in the crash event. The new dummy neck was modelled as a series of rigid bodies (representing the seven cervical vertebrae and the uppermost thoracic element, T1) connected by pin joints, and supplemented by two muscle substitutes. The joints had non-linear stiffness characteristics and the muscle elements possessed both elastic stiffness and damping properties. The new model was compared with two neck models with the same number of vertebrae, but without muscle substitutes. The properties of the muscle substitutes and the need of these were evaluated by using three different modified neck models. The motion of T1 in the simulations was prescribed using displacement data obtained from volunteer tests. In a sensitivity analysis of the mathematical model the influence of different factors on the head-neck kinematics was evaluated. The neck model was validated against kinematics data from volunteer tests: linear displacement, angular displacement, and acceleration of the head relative to the upper torso at 7 km/h velocity change. The response of the new model was within the corridor of the volunteer tests for the main part of the time history plot. This study showed that a combination of elastic stiffness and damping in the muscle substitutes, together with a non-linear joint stiffness, resulted in a head-neck response similar to human volunteers, and superior to that of other tested neck models.

Acceleration↗

[Pharmacokinetics of cyclophosphamide, adriamycin and adriamycin prodrug (HMR 1928) using an ex vivo isolated perfused human lung model (IHLP)].

BACKGROUND: Today knowledge about pharmacokinetics of anticancer drugs in human malignant tumors is poor. Data from in vivo studies are limited and difficult to obtain due to ethical aspects. An ex vivo isolated perfused and ventilated human lung model however allows pharmacological studies of human bronchial carcinoma inside their host organ, the lung, under physiological conditions without compromising the patient. METHODS: Following surgery for bronchial carcinoma human lung preparations were reperfused and ventilated extracorporally for 2-3 hours. During the reperfusion anticancer drugs are added to the perfusion solution and their uptake into tumor, normal lung tissue, and lymph nodes is studied. RESULTS: An initial study showed that lung reperfusion under physiological circumstances over a period of 2-3 hours did not interfere with histo-pathological diagnostics and staging; an important precondition for potential adjuvant treatment. Pharmacokinetics of cyclophosphamid, adriamycin, and a water soluble adriamycin prodrug (HMR 1826) were measured. Final tissue concentrations of adriamycin and cyclophosphamid in peripheral lung parenchyma turned out to be 10 times higher compared to tumor tissue. However, following perfusion with adriamycin prodrug final tissue concentrations of adriamycin were in the same range in lung and tumor. CONCLUSIONS: The ex-vivo isolated human lung perfusion model (IHLP) has proven to be an ideal scientific model for pharmacological investigations of human tumors as an intermediate step between cell culture and in-vivo situation without any disadvantage for the patient. The tumor-to-host interaction is completely saved in this model. However, first pass reactions of drugs in other organs must not play a role for the substances studied with the IHLP. The role and future applications of the isolated perfused human lung model for other indications is discussed.

Antineoplastic Agents↗

[Telomerase in lung cancer. Testing the activity of the "immortaligy enzyme" bronchial biopsies increases the diagnostic yield in cases of suspected peripheral bronchogenic carcinomas].

The proliferative capability is time-limited in normal somatic cells by the shortening of their chromosomal ends, the telomeres (Hayflick limit). An important feature of malignant cells is their immortality. The probably most common mechanism of tumour cells to achieve unlimited replicability is the activation of the enzyme telomerase. The reverse transcriptase can compensate the loss of telomeres. Using a PCR-based TRAP assay we found telomerase activity in tumour biopsies, exsudates and bronchial washings in various thoracic malignancies. In 38 of 47 patients with suspected peripheral lung cancer eventually surgery or invasive procedures proved a malignancy. In fluoroscopically guided bronchial brushings from 25 of these 38 patients (66%) the TRAP assay revealed telomerase activity. There was a single false positive case (tuberculosis) and with a single exception, the simultaneously taken brushes of the contralateral lobes were all telomerase negative. In 23 patients (61%) tumour cells were found in the cytological examination. In 33 patients at least one marker was positive. Thus the combination of cytology and telomerase test in bronchial brush biopsies attained a diagnostic yield of 87%.

Biopsy↗

[Mediastinoscopy in the staging of bronchial carcinoma--a critical assessment].

BACKGROUND: Mediastinoscopy has a high sensitivity for lymph node staging with a specificity of 100%. This compensates the disadvantage of being an invasive procedure compared to CT and PET scan. Although many studies examined the sensitivity, rate of complications and costs no data have been published concerning interindividual differences in relation to the surgeon performing the operation. METHODS: From 6/98 to 12/99 in a prospective study all biopsied lymph nodes were documented. Histopathologic results of mediastinoscopy and the following operation were correlated with the 6 participating surgeons. From these data the sensitivity of mediastinoscopy for preoperative lymph node staging was analysed. RESULTS: Analysis of 165 mediastinoscopies showed an overall sensitivity of 80.6%. 4.1 lymph nodes were biopsied per patient. Substantial differences were noted for individual biopsy patterns between surgeons, but surgeon-related sensitivity was similar. Lymph nodes 7 were reached in 15.2% to 90.9% and 2 left in 39.4% to 84.4%, whereas lymph nodes 4 were biopsied at similar rates by all surgeons. CONCLUSION: The variable "surgeon" can be neglected if a sufficient number of lymph nodes is biopsied. Despite individual biopsy patter mediastinoscopy has a higher sensitivity than CT scan and is still the method for choice of preoperative staging. Internal quality control in thoracic surgery departments is desirable.

Biopsy↗

Evaluation of the BioRID P3 and the Hybrid III in pendulum impacts to the back--a comparison to human subject test data.

The BioRID P3 (Biofidelic Rear Impact Dummy) and the Hybrid III were evaluated in pendulum impacts to the back and compared to data from previous cadaver tests. The test setup impacting seated cadavers was reproduced with a pendulum impacting seated dummies at the level of T6 (6th thoracic vertebra). The pendulum mass was 23 kg and the impact velocity 4.6 m/s. The results showed that the BioRID P3 was more biofidelic than the Hybrid III in terms of the peak responses and the temporal window of the head and head relative to T1 horizontal, vertical, and angular displacement. This study is an evaluation of both the BioRID P3 and the Hybrid III against a recently available set of human subject data. The study meets the need for validation of the BioRID P3 at a higher impact severity than has been previously accomplished.

Acceleration↗

Tonsillectomy or tonsillotomy?--A randomized study comparing postoperative pain and long-term effects.

BACKGROUND: tonsillectomy (TE) is currently the most common treatment for children with snoring and sleep apnea. Many of these children have not had any severe throat infections. To cure such children from their obstructive problems, without influencing the immunological function of the tonsils, tonsillotomy (TT) with CO2-laser was performed in a randomized study comparing it to regular tonsillectomy, with special attention to postoperative pain and symptom recurrence. METHOD: 41 children 3.5-8 years-old were included--21 'TT's' and 20 'TE's'. They were all operated under the same anesthesia and followed the same postoperative scheme for analgesia. A visual analogue scale for pain measurements with faces was used for the first 24 h. After that, each day until pain-free, the parents registered the child's pain on a three graded scale, what the child was able to eat, and the amount of analgesic drugs used. RESULTS: all the children were cured from their breathing obstruction. The mean time used for the surgery was the same and no postoperative bleeding was seen in either group. 'TT children' were pain-free after 5 days and 'TE children' after 8 days. Eight to ten days after surgery, the TT-children had gained weight and the TE children lost weight significantly. The TE group used twice as much analgesic drugs as the TT group during the first postoperative week. The TT group was healed with normal-looking, but small tonsils after 8-10 days; the TE group often still showed edema and crusts. At the one-year follow-up 2/21 among the 'TT-children' snored, but did not require re-surgery. CONCLUSION: tonsillotomy is much less painful than TE and children recover more quickly. Results with respect to breathing obstruction are almost the same for both methods at 1-year follow-up.

Child↗

Using the carbon dioxide laser for tonsillotomy in children.

Carbon dioxide laser tonsillotomies were performed on 33 children aged 1-12 years for the relief of obstructive symptoms due to tonsillar hyperplasia. As opposed to conventional tonsillectomy, only the protruding part of each tonsil was removed. A carbon dioxide laser delivering 20 W was used for the excision. Twenty-one children were seen in active short-term follow-up and the records of all the children were checked for possible surgery related events up to 20-33 months after surgery. Laser tonsillotomy was uniformly effective in relieving the obstruction, with good hemostasis. The tonsillar remnants healed completely within 2 weeks. No major adverse events occurred. Post-operative pain appeared slight and easily controlled. There was no gain in operating time compared with conventional tonsillectomy. The laser tonsillotomies were in most cases done in day surgery. No recurrence of obstructive problems was reported up to 20-33 months after surgery. It was concluded that tonsillotomy, using a carbon dixoide laser, is a valid treatment for obstructive symptoms caused by enlarged tonsils, which can be performed with little bleeding and post-operative pain. The improved hemostasis may enable a shift from in-patient to day surgery.

Acetaminophen↗

Novel polymer substrates for SFM investigations of living cells, biological membranes, and proteins.

Extended studies were performed to prepare substrates for scanning force microscopy of biological samples with a surface roughness below 1 nm rms over an area of 500 x 500 nm2. The substrate smoothness and the lack of tip obscuring material are indispensable in order to visualize detailed structures of membrane surfaces, particularly when scanning the lamellipodia of mechanically sensitive goldfish glial cells where peripheral lamellipodia are only 20-30 nm in thickness. Appropriate substrates are poly(vinyl phenyl ketone) or furan polymers with corrugations of 0.3 and 0.15 nm rms, respectively, to which the growth-promoting protein laminin adsorbs directly with an acceptably increased roughness. Cells show normal growth behavior on these substrates and stick to the substrates in a stable fashion during several scans. Thus details of the membrane's surface may be resolved and are not obscured by the substrate texture. The uncoated furan polymer substrates are suitable for immobilization of membrane preparations such as purified membrane fragments containing bacteriorhodopsin or Na, K-ATPase and protein preparations such as antibodies.

3T3 Cells↗

[Thoracoscopy versus thoracotomy. The dilemma of the comparison and its meaning for quality assurance in thoracic surgery].

The need for scientific investigation into the benefits of thoracoscopy in comparison to thoracotomy as well as State intervention to assure quality in the field of surgery motivated the members of the commission of endoscopic surgery of the German Society of Thoracic Surgery to conduct a pilot project at their hospitals. This pilot project was expected to analyse data on the outcome and a selection of variables concerning trauma and postoperative quality of life of some 400 patients treated between 8/95 and 10/95 at 5 thoracic surgical clinics. On completion of the pilot project the course of 141 patients undergoing different thoracic operations at 4 thoracic surgery departments had been documented to various degrees. 60 patients for various indications received a thoracoscopy, 72 a thoracotomy. In 9 patients thoracoscopy was converted to thoracotomy (6.4%). Eight of the 141 patients died in the postoperative course (5.7%), overall morbidity was 15.6%. There was a slight but statistically not significant difference concerning mortality and morbidity in favor of thoracoscopy (1.7 vs. 9.7% and 10 vs. 19.4%). But, there was a selection of malignant diseases, higher age and high risk patients towards thoracotomy. In subgroups of patients undergoing operations not bigger than the resection of three lung wedges only time of operation and length of incision revealed to be significantly shorter for thoracoscopy (69(25-190) min vs. 128(24-240)min, p = 0.0013; 6(4-8)cm vs. 23(12-35)cm, p = 0.0001). Borderline significance was reached by the Spitzer-Index in advantage for thoracoscopy (8(2-10)points vs. 7(0-10)points, p = 0.0728). Thoracotomy and thoracoscopy are access procedures used with different indications in different patients. Differences concerning trauma and quality of life if present are marginal and will need studies to be outlined. Quality assurance in thoracic surgery using a standardized documentation will not succeed under the given circumstances.

Adult↗

Enhanced uptake of doxorubicin into bronchial carcinoma: beta-glucuronidase mediates release of doxorubicin from a glucuronide prodrug (HMR 1826) at the tumor site.

Lack of tumor selectivity is a severe limitation of cancer chemotherapy. Consequently, reducing dose-limiting organ toxicities such as the cardiac toxicity of doxorubicin (Dox) is of major clinical relevance. Approaches that would facilitate a more tumor-selective anticancer therapy by using nontoxic prodrugs that are converted to active anticancer agents at the tumor site have been the subject of intensive research. One potential method to overcome the cardiac toxicity of Dox is to apply a nontoxic, glucuronide prodrug (HMR 1826) from which Dox is released by the action of beta-glucuronidase, an enzyme present at high levels in many tumors. Using a recently developed, isolated, perfused human lung model, we compared the uptake of Dox into normal lung and lung tumors after a 2.5-h lung perfusion with doxorubicin (n = 8) and with the novel doxorubicin glucuronide prodrug (n = 8). Dox showed a poor uptake into lung tumors as compared with normal lung [mean Dox concentration at the end of perfusion, 1.78 +/- 3.11 (median, 0.66) microg/g versus 22.03 +/- 10.4 (median, 18.5) microg/g; P < 0.001]. However, after perfusion with HMR 1826, the level of Dox in tumor tissue was about 7-fold higher than after perfusion with Dox itself [14.04 +/- 12.9 (median, 12.9) microg/g versus 1.78 +/- 3.11 (median, 0.66) microg/g, P < 0.05, n = 8]. In vitro experiments showed a significantly higher beta-glucuronidase expression and activity in the tumors. The extent of in vitro cleavage of HMR 1826 by homogenized lung tissue was closely related to the content of beta-glucuronidase (r = 0.9834, P < 0.0001). When D-saccharolactone, a specific inhibitor of beta-glucuronidase, was added to the perfusate containing HMR 1826, no accumulation of Dox in lung tissue was seen. These data indicate that the high Dox levels achieved in the tumors with HMR 1826 resulted from cleavage of the prodrug by beta-glucuronidase at the tumor site. Thus, the problem of poor Dox uptake into lung tumors could be circumvented by applying the doxorubicin glucuronide prodrug. Several lines of evidence based on both ex vivo and in vitro results indicate that the approach described using a glucuronide prodrug may be useful in facilitating more selective delivery of chemotherapy to tumors in humans.

Aged↗

Laryngologic management of infants with the Chiari II syndrome.

As a part of a prospective multi-disciplinary study, all children born with a Chiari II malformation within the Uppsala region during a 3-year period were evaluated for any difficulties in breathing or swallowing. The evaluation was repeated at regular intervals during their first 18 months. Direct laryngoscopies were performed using flexible fiberscopes. Four out of 22 children were found to have disturbed breathing. Among those, two suffered from central apnoeic spells as well as bilateral vocal fold motion impairment, one from apnoeic spells only and one from bilateral vocal fold motion impairment only. All four also had dysphagia with aspiration. Three of the children developed respiratory symptoms within the first 3 months and the symptoms of the fourth begun within the first 6 months. One infant with severe symptoms expired at the age of 3 months. The vocal fold paralysis, apnoeic spells and swallowing difficulties of another infant resolved following active neurosurgical management. The conclusion that laryngologic issues are prominent in the severe Chiari II syndrome was further supported by a review of four more cases managed in recent years. Laryngologic assessment in the neonatal period can help to raise the issue of early neurosurgical intervention as well as identify some of the infants who will need extensive habilitation. Screening of laryngeal function by means of flexible fiberoptic laryngoscopy is recommended.

Apnea↗