Biomedical subjects

S Thomsen

Publications and source records attributed to S Thomsen.

At least 37 records · Page 2Linked to original sources

PubMed1998

Murine leukemia virus recombinants that use phosphate transporters for cell entry induce similar spongiform encephalomyelopathies in newborn mice.

Amphotropic Moloney-murine leukemia virus recombinants (Mo-AmphoV) induce a severe spongiform encephalomyelopathy in newborn mice. We show here that a coisogenic recombinant with a 10A1-MuLV host range (Mo-10A1V) also induces a neurodegenerative disease, clinically characterized by mild tremor and ataxia. Spongiform lesions are most severe in the metencephalon and mesencephalon but extend into the prosencephalon and spinal cord. Significantly, the quality of histopathology was indistinguishable between Mo-AmphoV and Mo-10A1V, probably reflecting a final common pathogenic pathway. Common receptor use thus may be an important determinant in the pathogenicity of these viruses. These results have implications for the clinical use of retroviral pseudotypes that use phosphate transporters for cell entry.

3T3 Cells↗

PubMed1998

Physiological and pathological factors of human breast disease that can influence optical diagnosis.

The 'normal' human female breast is a very complex organ that changes considerably during development, pregnancy and menopause. In addition, it is an excretory organ that, during lactation, discharges various metabolites and certain drugs that can be optically active. Optical diagnosis of breast cancers requires detection of differential concentrations of 1) various absorbers and scatterers or 2) native or exogenous fluorophores to distinguish cancers from surrounding 'normal' and benign breast tissues. The differential concentrations are due to the biology of the cancer cells and the host responses to the cancer growth. For most patients, the cancer will be intermixed with a complex 3-dimensional array of 'normal' breast tissue and benign breast lesions. This complexity will challenge the optical biopsy investigator but, with the recent advances in our understanding of light transport, optical diagnostic techniques and devices can be developed to complement and supplement current breast cancer screening techniques.

Breast↗

PubMed1998

Controlled radiofrequency endotubal sterilization.

STUDY OBJECTIVE: A safe, effective, inexpensive method of transcervical tubal sterilization could have a major impact on women's health. In this study, we evaluated the efficacy of a new radiofrequency catheter prototype designed for endotubal sterilization using animal models. SETTING: Animal research laboratory. DESIGN: Prospective observational study. METHOD: The optimal energy delivery to create a complete circumferential transmural thermal lesion in the tube was determined in 114 in vitro acute studies using porcine and bovine fallopian tubes. A study was then initiated with eight mini-pigs. Thirty-four lesions were made in the fallopian tubes using computer-controlled power delivery. Three weeks later the animals were euthanized and evaluated. MEASUREMENTS AND MAIN RESULTS: A hydrosalpinx was evident in 8/11 of the tubes with separate proximal and distal cautery, implying occlusion at each of these sites. Complete occlusion of the tubes was seen at 12/22 sites evaluated by histology. Narrowing was seen in 9/22, and 1/22 was open. CONCLUSION: The endotubal cautery prototype creates a reproducible lesion, but did not always cause complete closure of the tube in this preliminary study. However, based on our results, we hypothesize that a radiofrequency catheter can be developed for minimally invasive transcervical sterilization.

Animals↗

PubMed1998

Entry of amphotropic and 10A1 pseudotyped murine retroviruses is restricted in hematopoietic stem cell lines.

Although transduction with amphotropic murine leukemia virus (MLV) vectors has been optimized successfully for hematopoietic differentiated progenitors, gene transfer to early hematopoietic cells (stem cells) is still highly restricted. A similar restriction to gene transfer was observed in the mouse stem cell line FDC-Pmix compared with transfer in the more mature myeloid precursor cell line FDC-P1 and the human erythroleukemia cell line K562. Gene transfer was not improved when the vector was pseudotyped with gp70SU of the 10A1 strain of MLV, which uses the receptor of the gibbon ape leukemia virus (Pit1), in addition to the amphotropic receptor (Pit2). Although 10A1 and amphotropic gp70SU bound to FDC-P1, K562, and fibroblasts, no binding to FDC-Pmix cells was detected. This indicates that FDC-Pmix cells lack functional Pit2 and Pit1 receptors. Pseudotyping with the vesicular stomatitis virus G protein improved transduction efficiency in FDC-Pmix stem cells by 2 orders of magnitude, to fibroblast levels, confirming a block to retroviral infection at the receptor level.

Animals↗

PubMed1998

Lack of functional Pit-1 and Pit-2 expression on hematopoietic stem cell lines.

Hematopoietic stem cells (HSC) are an important target for retroviral gene transfer. However, transduction efficiency in these HSC is extremely low compared to fibroblasts or more mature hematopoietic cells. This infection block was analyzed in the HSC line FDC-Pmix. The infection frequency with the amphotropic murine leukemia virus (MLV-A) is more than 100-fold lower in FDC-Pmix cells as compared to fibroblasts. Pseudotyping with the env of the 10A1 strain (MLV-10A1), which uses both the amphotropic receptor (Pit-2) and the receptor for gibbon ape leukemia virus (Pit-1), did not improve the infection efficiency. Vectors pseudotyped with VSV G protein were found to overcome the infection block in FDC-Pmix, confirming that the block is at the level of virus binding and possibly penetration. Accordingly, we could not detect virus binding of MLV-A or MLV-10A1 to FDC-Pmix cell lines. Northern blot analysis was performed to detect whether the defect is at the level of transcription. Surprisingly, similar levels of Pit-2 receptor transcripts were detected in all cell types. The overexpression of rat Pit-2 DNA in CHO but not in FDC-Pmix cells improved amphotropic infection frequency after introducing rat Pit-2 DNA into the cells. Taken together these results show that the inefficient infection of FDC-Pmix is due to a lack of functional receptors. Either the receptor protein is incorrectly processed in these cells or a cofactor is missing in FDC-Pmix cells that is necessary for efficient binding and/or penetration.

Animals↗

PubMed1998

Predictors of a healthy workplace for Swedish and English psychiatrists.

BACKGROUND: Few studies have attempted to analyse the organisational aspects of the workplace that may affect the well-being of psychiatrists and even fewer have offered insights into what a positive workplace might look like. This study provides an outline of such a workplace, with reference to individual and organisational factors. In addition, a comparison is made between two European cities to check for cultural differences. METHOD: Three hundred and eighty psychiatrists from Stockholm and Birmingham responded to a previously tested questionnaire on their work environment. RESULTS: Predictors of a positive workplace for psychiatrists were: high self-esteem, satisfactory support with work-related problems, lower perceived workload, positive view of leadership, low work-related exhaustion and having a sense of participation in the organisation. There were few cultural differences. CONCLUSIONS: Measures should be taken to improve leadership skills for managers, to offer more support for work-related problems, and to allow psychiatrists to participate more in the organisation.

Anxiety↗

PubMed1998

Near-infrared Raman spectroscopy for in vitro detection of cervical precancers.

In this study, we investigate the potential of near-infrared Raman spectroscopy to differentiate cervical precancers from normal tissues, inflammation and metaplasia and to differentially diagnose low-grade and high-grade precancers. Near infrared Raman spectra were measured from 36 biopsies from 18 patients in vitro. Detection algorithms were developed and evaluated relative to histopathologic examination. Algorithms based on empirically selected peak intensities, ratios of peak intensities and a combination of principal component analysis for data reduction and Fisher discriminant analysis for classification were investigated. Spectral peaks were tentatively identified from measured spectra of potential chromophores. Empirically selected normalized intensities can differentiate precancers from other tissues with an average sensitivity and specificity of 88 +/- 4% and 92 +/- 4%. Ratios of unnormalized intensities can differentiate precancers from other tissues with a sensitivity and specificity of 82% and 88% and high-grade from low-grade lesions with a sensitivity and specificity of 100%. Using multivariate methods, intensities at eight frequencies can be used to differentiate precancers from all other tissues with a sensitivity and specificity of 82% and 92% in an unbiased test. Raman algorithms can potentially separate benign abnormalities such as inflammation and metaplasia from precancers. Comparison of tissue spectra to published and measured chromophore spectra indicate that the most likely primary contributors to the tissue spectra are collagen, nucleic acids, phospholipids and glucose 1-phosphate. These results suggest that near-infrared Raman spectroscopy can be used for cervical precancer diagnosis and may be able to accurately separate samples with inflammation and metaplasia from precancer.

Cervix Uteri↗

PubMed1997

Controlled temperature tissue fusion: argon laser welding of rat intestine in vivo. Part one.

BACKGROUND AND OBJECTIVE: Thermal denaturation of proteins is recognized as a rate process governed by the local temperature-time response. Since rate processes are exponential with temperature, laser-assisted tissue welding was performed with and without temperature feedback control (TFC) to investigate the efficacy of temperature feedback in enhancing the photothermal welding process in vivo. STUDY DESIGN/MATERIALS AND METHODS: An automated system was developed for temperature feedback controlled laser irradiation. An experimental device incorporating co-aligned laser delivery and temperature detection was used to perform argon laser welded (with and without TFC) enterotomies. The weld strength and histology of laser welded and control sutured enterotomies were compared in an in vivo rat model. Animals (n = 41) were sacrificed at 1, 3, 7, and 21 days postoperatively, and the anastomotic site was removed for bursting/leaking pressure measurements and histological examination. RESULTS: Laser-welded (with and without TFC) and control sutured anastomoses in surviving animals healed comparably. Some laser-welded anastomoses without TFC ruptured spontaneously (4 out of 15) leading to the animals' death within the first 24-36 hours postoperatively. None of the animals in the other groups had this problem (control suture 0/6; laser with TFC 1 leak/8). The bursting/leaking pressures of the laser welded anastomoses were not significantly different than those of the sutured controls. CONCLUSION: TFC improves the quality of laser-welded rat intestinal anastomoses in vivo in the critical first postoperative 36 hours.

Anastomosis, Surgical↗

PubMed1997

Controlled temperature tissue fusion: Ho:YAG laser welding of rat intestine in vivo. Part two.

BACKGROUND AND OBJECTIVE: Temperature feedback control (TFC) during laser-assisted tissue welding was implemented to eliminate exponential increases in the rate of denaturation associated with rapidly increasing temperatures. This study was undertaken to investigate and compare the weld strengths and healing responses of laser welded enterotomies with and without TFC using a cw Ho:YAG laser and to examine the effects of wavelength on weld strength and histology. The Ho:YAG experimental results were compared with a similar study using cw argon ion laser irradiation. STUDY DESIGN/MATERIALS AND METHODS: An automated system was developed for temperature feedback controlled laser irradiation. An experimental device incorporating co-aligned laser delivery and temperature detection was used to perform cw Ho:YAG laser-welded enterotomies (with and without TFC). The weld strength and histology of laser welded and control sutured enterotomies were compared in an in vivo rat model (Ho:YAG, n = 42; argon, n = 41). Animals were sacrificed at 1, 3, 7, and 21 days postoperatively and the anastomotic site was removed for bursting/leaking pressure measurements and histological examination. RESULTS: Argon and Ho:YAG laser-welds with and without TFC and the control sutured anastomoses healed comparably, although wound abscesses were more prevalent in the Ho:YAG group leading to delay in mucosal healing. Laser-welded anastomoses without TFC were associated with more spontaneous ruptures and leaks (argon: 4/6 ruptures; Ho:YAG: 1/4 leak, 2/4 ruptures, & 1/3 stenosis) during the survival period than those with TFC (argon: 1/3 leak; Ho:YAG: 1/5 rupture). Bursting pressures of the Ho:YAG welds were weaker at 1 week than the argon welds, but by 3 weeks, laser welds and suture anastomoses were equally strong. CONCLUSION: From the spontaneous failure rates encountered, it is believed that TFC improves the quality and stability of laser-assisted enterotomy closures in surviving animals. However, TFC does not provide a satisfactory method to identify completion of a weld.

Anastomosis, Surgical↗

PubMed1996

[Esophageal perforations].

An oesophageal perforation is a serious condition with high morbidity and mortality. During the latest decades an increased number of traumatic perforations as well as wide use of endoscopic procedures have increased the incidence of oesophageal perforation. An early diagnosis and treatment is important for the prognosis. Cervical and selected thoracic perforations can be treated conservatively although the majority should be operated. Primary closure can be performed if done before 24 hours have elapsed, while later treatment is controversial. Drainage of the mediastinum and pleural space, as well as diversion of saliva and gastric content is important. The literature is reviewed in relation to etiology, diagnosis, treatment and prognosis.

Esophageal Perforation↗

PubMed1996

[Benign esophageal perforations treated at a department of thoracic surgery].

Between January 1, 1980 and December 31, 1994, 37 patients with benign oesophageal perforation underwent different kinds of treatment. The overall mortality was 30%. When diagnosed less than 12 hours after the perforation the mortality was 21%, between 12 and 24 hours. Reinforced primary repair gave the best results without any deaths in seven cases where it was performed. Oesophageal perforation is a serious condition, and it is important to know the symptoms. If there is any suspicion of the condition, an oesophageal X-ray with watersoluble contrast medium should be performed on liberal indication. When diagnosed the patient should be transferred to a Department of Thoracic Surgery immediately. Only few patients can be treated conservatively and most should be operated with reinforced primary suture and drainage.

Adolescent↗

PubMed1996

Controlled temperature tissue fusion: argon laser welding of canine intestine in vitro.

BACKGROUND AND OBJECTIVE: Thermal denaturation of proteins is recognized as a rate process governed by the local temperature-time response and is believed to be the principal mechanism for photothermal tissue welding. Since rate processes are exponential with temperature, feedback control of tissue surface temperature is hypothesized to create a quasi-constant rate of denaturation that will enhance the tissue welding process. STUDY DESIGN, MATERIALS AND METHODS: Controlled temperature tissue welding of severed edges of fresh canine jejunum was performed in vitro by remote sensing of tissue surface temperature with an infrared sensor. A hardware controlled temperature feedback system opened and closed a shutter located in the beam path of an argon ion laser to provide constant temperature welding. RESULTS: Strong tissue fusion was not possible at or below a surface temperature of 70 degrees C, but was accomplished at 80 degrees, 90 degrees, and 95 degrees, and 100 degrees C. Fusion was achieved with thermal coagulation of the collagenous submucosa and mucosal tissues. The bursting strength of welds created at 90 degrees C and 95 degrees C were significantly stronger than those performed at 80 degrees C. CONCLUSION: Laser-assisted intestinal anastomoses created in vitro are optimally strong at 90-95 degrees C feedback control temperatures.

Animals↗

PubMed1996

Development of a multivariate statistical algorithm to analyze human cervical tissue fluorescence spectra acquired in vivo.

BACKGROUND AND OBJECTIVE: A general multivariate statistical algorithm has been developed to analyze the diagnostic content of cervical tissue fluorescence spectra acquired in vivo. MATERIALS AND METHODS: The primary steps of the algorithm are to: (1) preprocess the data to reduce inter-patient and intra-patient variation of tissue spectra within a diagnostic category, without a priori information, (2) dimensionally reduce the preprocessed fluorescence emission spectrum with minimal information loss and use it to select the minimum number of the original emission variables of the fluorescence spectrum required to achieve classification with negligible decrease in predictive ability, and (3) assign a posterior probability to the diagnosis of each sample, so that samples with relative uncertain diagnosis can be reevaluated by a clinician. The algorithm was tested retrospectively and prospectively on cervical tissue spectra acquired from 476 sites from 92 patients at 337 nm excitation. RESULTS: The algorithm based on the entire fluorescence spectrum differentiates squamous intraepithelial lesions (SILs) from normal squamous epithelia and inflammation with an average sensitivity and specificity of 88% +/- 1.4 and 70% +/- 1, respectively. The average sensitivity and specificity of the identical algorithm based on intensity selected at only two emission wavelengths is 88% +/- 1.4 and 71% +/- 1.4, respectively. CONCLUSION: The multivariate statistical algorithm based on both types of spectral inputs at 337 nm excitation has a similar sensitivity and significantly improved specificity relative to colposcopy in expert hands.

Algorithms↗

PubMed1996

Spectroscopic diagnosis of cervical intraepithelial neoplasia (CIN) in vivo using laser-induced fluorescence spectra at multiple excitation wavelengths.

BACKGROUND AND OBJECTIVE: The diagnostic contribution of cervical tissue fluorescence spectra acquired in vivo at 380 and 460 nm excitation were analyzed using a general multivariate statistical algorithm. MATERIALS AND METHODS: The primary steps of the algorithm are to: (1) preprocess data to reduce interpatient and intrapatient variation of tissue spectra from the same diagnostic category, without a priori information, (2) dimensionally reduce the pre-processed spectral data using Principal Component Analysis, and (3) develop a probability based classification scheme based on logistic discrimination using the diagnostically useful principal components. The algorithm was tested on cervical tissue spectra acquired from 165 sites at 380 nm excitation and from 147 sites at 460 nm excitation. A retrospective and prospective estimate of the algorithm's performance was determined. RESULTS: At 460 nm excitation, (1) SILs can be differentiated from normal squamous tissues with an average sensitivity and specificity of 91% +/- 1.3 and 75.5% +/- 1, respectively; furthermore, (2) high grade SILs can be differentiated from low grade SILs with an average sensitivity and specificity of 80% +/- 4 and 76% +/- 5, respectively. In addition, using tissue spectra at 380 nm excitation, SILs can be differentiated from normal columnar epithelia and inflammation with an average sensitivity and specificity of 77% +/- 1 and 72% +/- 9, respectively. CONCLUSIONS: Fluorescence spectra at multiple excitation wavelengths are essential for the detection and differential diagnosis of SILs at colposcopy.

Algorithms↗

PubMed1995

Lifetime testing of sapphire and sculpted silica fiber scalpels.

BACKGROUND AND OBJECTIVE: Sapphire and sculpted silica fiber scalpels were evaluated for performance as they aged. Performance was determined by measuring their useful lifetime, forward transmission, incision depth, and the thermal coagulation thickness at the sides and bottom of the incision. STUDY DESIGN/MATERIALS, AND METHODS: Aging was performed with a chicken breast model. Performance measurements were made at periodic intervals. Sapphire scalpels were cooled with air or saline. RESULTS: The air-cooled, frosted sapphire scalpels had the longest useful lifetime, whereas the saline-cooled, frosted sapphire scalpels had the shortest. Aging deteriorated the forward transmission of the sculpted silica fiber scalpels the most. Little difference was found between the averages of all incision measurements. Two of the saline-cooled, frosted sapphire scalpels fractured during the aging process. CONCLUSION: Aging influences the scalpel lifetime, but there was no evidence that the aging process significantly affected the incision size.

Aluminum Oxide↗

PubMed1995

Corneal photocoagulation with continuous wave and pulsed holmium: YAG radiation.

In this study, the effectiveness of pulsed and continuous wave (CW) holmium: YAG lasers in coagulating in vitro pig corneas was analyzed. With the CW laser, irradiance and exposure time were varied; irradiance, from 162 to 324 W/cm2 and exposure time, from 200 to 800 ms. With the pulsed laser, number of pulses and radiant exposure were varied; number of pulses per lesion, from 4 to 30 and radiant exposure, from 10 to 25 J/cm2. Laser-induced corneal damage was determined by analyzing histological cross sections of each lesion. Depth and diameter of the lesions were plotted against the varying laser parameters. Light and birefringent photomicrographs of typical lesion histology show that the pulsed laser significantly damaged superficial layers of the cornea and could not achieve the coagulation depths produced by the CW laser. Additional histology demonstrates that minimal surface damage (intrastromal coagulation) occurred when the CW laser beam was delivered with a sapphire-tipped contact probe. The results provide empirical data on the sensitivity of each parameter in producing a range of coagulation end points. In addition, the experimental results describe trends between the parameters of either laser and the extent of coagulation.

Animals↗

PubMed1995

In vivo autofluorescence of an unpigmented melanoma in mice. Correlation of spectroscopic properties to microscopic structure.

Recently, fluorescence spectroscopy and imaging have been under investigation for in vivo diagnosis of several types of superficial cancer, including primary melanomas of the skin. Here we report on a detailed investigation of the autofluorescence properties of a K1735P melanoma implanted intradermally in the ears of syngeneic C3H/HeN mice. Although this tumour can produce melanin in some cases, it appeared as an unpigmented lesion in our experiments. Excitation-emission maps in the wavelength range of 360-700 nm were recorded from tumours and normal ears. The control ears and the tumour-bearing ears showed fluorescence in a broad range of excitation and emission wavelengths. Valleys of decreased fluorescence were observed in the 385-425 nm range and could be related to absorption of the excitation light by haemoglobin, oxyhaemoglobin and a third unknown absorber. The spectroscopic differences between the malignant melanoma and the control skin could be related to either differences in blood oxygenation or the tissue dimensions. However, no spectroscopic features were detected reflecting intrinsic differences between the melanoma and normal tissue.

Animals↗

PubMed1995

Combined ultrasound and fluorescence spectroscopy for physico-chemical imaging of atherosclerosis.

This paper describes a combined ultrasonic and spectroscopic system for remotely obtaining physico-chemical images of normal arterial tissue and atherosclerotic plaque. Despite variations in detector-tissue separation, R, fluorescence powers corresponding to pixels in the image are converted to the same set of calibrated units using distance estimations from A-mode ultrasound reflection times. An empirical model, validated by Monte Carlo simulations of light propagation in tissue, is used to describe changes in fluorescence power as a function of R. Fluorescence spectra of normal and atherosclerotic human aorta obtained with this system are presented as a function of R. To compensate for changes in fluorescence power with R, the empirical model was used in each case to calculate the fluorescence power at a constant reference value of R(Rref = 1.67 mm). Prior to compensation, tissue fluorescence power decreased more than a factor of two as R was increased from 2.5 to 5 mm. Following compensation, the fluorescence power varied less than +/- 10% of the average compensated peak. The chemical composition of each sample was determined by fitting its fluorescence spectrum (in calibrated units) to a model of tissue fluorescence incorporating structural protein and ceroid fluorescence, as well as structural protein and hemoglobin attenuation. Parameters of the fit were used to classify tissue type. Without compensation for distance variation, classification of tissue type was frequently incorrect; however, with compensation, predictive value was high. A 1-D chemical image of a section of human aorta containing both normal and atherosclerotic regions obtained with this system is also presented. After compensation for detector-sample separation, tissue classifications along the cross-section closely resemble those obtained from histology. Regions of elevated ceroid concentration and intimal thickening are clearly observable in the resultant chemical image. The potential value of this type of system in the diagnosis and treatment of coronary artery disease is discussed.

Aorta↗