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S Holm

Publications and source records attributed to S Holm.

At least 37 records · Page 2Linked to original sources

The privacy of Tutankhamen--utilising the genetic information in stored tissue samples.

Recent technical developments in genetic testing has led to a situation where the DNA in previously stored tissue samples can be extracted and used for genetic analysis. This raises the question of how to decide whether a specific use of such samples should be allowed. Using the genetic testing of ancient DNA in general, and the DNA of the pharaoh Tutankhamen in particular as examples this paper analyses the question. It investigates whether ethical frameworks based on proxy consent, cultural affiliation, ownership, or the privacy rights of the dead are appropriate and justifiable in this context. The conclusion is that frameworks based on proxy consent, cultural affiliation, and ownership are not very useful.

Austria↗

Transcranial Doppler sonography and internal jugular bulb saturation during hyperventilation in patients with fulminant hepatic failure.

Mechanical hyperventilation is often used to postpone or ameliorate intracranial hypertension in patients with fulminant hepatic failure (FHF). Because such treatment may critically reduce cerebral blood flow (CBF), bedside techniques to monitor CBF are warranted. In this study, we evaluated the efficacy of transcranial Doppler (TCD) sonography of the middle cerebral artery (MCA) and internal jugular bulb saturation (svJO(2)) to determine relative changes in CBF during mechanical hyperventilation in 8 patients with FHF (median age, 40 years; range, 20 to 54 years). We found that TCD and svJO(2) decreased during hyperventilation in parallel with CBF, determined by the xenon 133 ((133)Xe) washout technique. Quantitatively, the TCD method was less accurate to determine carbon dioxide (CO(2)) reactivity compared with svJO(2) and the (133)Xe technique. This indicates a slight change in MCA diameter during hyperventilation. We conclude that TCD and svJO(2) monitoring may give valuable information on relative changes in CBF during hyperventilation. However, the TCD method appears less accurate for quantitative estimation of CO(2) reactivity in patients with FHF.

Adult↗

Growth of costochondral grafts in reconstruction of the mandibular condyle: an experimental study in domestic pigs.

Reconstruction of the mandibular condyle with costochondral grafts (CCGs) in children may result in overgrowth at the reconstructed side of the mandible. In this study we report on the effects of functional stimuli on growth and morphology of growth plates of CCGs used for immediate mandibular condyle replacement in 10 juvenile pigs. The mandibular condyles were resected unilaterally and immediately reconstructed with autogenous CCGs. Another CCG was placed submuscularly on one tibia. The lengths of both CCGs and of one rib before resection were measured at operation and 12 weeks later. The grafts were labelled with intraperitoneal injections of oxytetracycline and alizarin eight and 12 weeks postoperatively, respectively. The extent of growth of the CCGs in the two environments was similar, so we concluded that the functional stimuli in the TMJ environment had only a minor influence on the extent of growth of the CCGs. The morphology of the growth plate of the CCGs had changed considerably.

Animals↗

In vivo measurement of haloperidol affinity to dopamine D2/D3 receptors by [123I]IBZM and single photon emission computed tomography.

This study examines the feasibility of a steady-state bolus-integration method with the dopamine D2/D3 receptor single photon emission computer tomography (SPECT) tracer, [123I]IBZM, for determination of in vivo affinity of haloperidol. The nonspecific binding of [123I]IBZM was examined in the rat brain by infusion of haloperidol to plasma levels approximately 100 times the Kd level in man. In humans, Kd for haloperidol binding was measured in four healthy volunteers that were examined twice: once with partial dopamine D2/D3 receptor blockade obtained by a scheduled infusion of unlabeled haloperidol (0.7 mg total dosage), and once in an unblocked state. Blood sampling and SPECT were performed intermittently during 6 hours after intravenous [123I]IBZM bolus injection. Plasma [123I]IBZM was determined by octane extraction. Plasma haloperidol was determined by a radioimmunoassay, and plasma protein binding was determined by equilibrium dialysis. In humans, the striatal D2/D3 receptor occupancy was 0.27+/-0.085 and the in vivo Kd for haloperidol was 0.25+/-0.1 nmol/L, which is comparable to Kd values as obtained from in vitro studies. The authors conclude that steady-state [123I]IBZM SPECT studies allow for determination of dopamine D2/D3 receptor occupancy in striatum and in vivo measurement of drug affinity to striatal dopamine D2 and D3 receptors.

Adult↗

The (18)F-fluorodeoxyglucose lumped constant determined in human brain from extraction fractions of (18)F-fluorodeoxyglucose and glucose.

Quantification of regional cerebral glucose metabolism (CMRglc) using positron emission tomography and 18F-fluorodeoxyglucose (PET-FDG) requires knowledge of the correction factor between FDG and glucose net clearance, the FDG lumped constant (LC). Because diverging values for LC have been obtained, the authors reevaluated LC by measuring the ratio of the cerebral net extraction fractions of FDG (E*) and glucose (E) from arteriovenous cerebral measurements. Thirty subjects were studied (mean age = 25 +/- 4 years): 12 during a programed infusion of FDG and 18 after a bolus injection of FDG. In the infusion study, LC was calculated as the ratio E*/E. In the bolus study, E* was calculated from the slope of a Patlak-Gjedde plot. Lumped constant was significantly smaller in the infusion study as compared with the bolus study (0.48 +/- 0.16 vs. 0.81 +/- 0.27, P < 0.001). In 4 subjects studied during continuous FDG infusion for 2.5 hours, LC decreased to 0.36 +/- 0.11. These results suggest that the "steady-state" method underestimates LC because E* continues to decline because of significant labeled product. Further, the authors provide evidence for resetting of LC toward a greater value. The subsequent resetting of CMRglc provides a physiologically more meaningful estimate and allows for comparison of CMRglc values between different methodologies.

Brain↗

Using (10)CO2 for single subject characterization of the stimulus frequency dependence in visual cortex: a novel positron emission tomography tracer for human brain mapping.

Carbon-10-labeled carbon dioxide ((10)CO2) with a half-life of 19.3 seconds offers almost ideal characteristics as a positron emission tomography (PET) tracer for assessment of the regional cerebral blood flow (rCBF) distribution, enabling multiple independent measurements at short intervals. To appraise the feasibility of (10)CO2 for localizing and characterizing human brain function in single subjects, the authors chose a well-characterized activation paradigm. In 6 healthy volunteers, 50 to 64 independent PET scans of the rCBF distribution were acquired while viewing an annular reversing checkerboard presented at 10 reversal frequencies between 0.03 and 30 Hz. Changes in regional cerebral activity as a function of reversal frequency were modeled in every subject using a set of polynomial basis functions, which, as predicted, showed highly significant second or third order relations located in the striatal cortex. Correlation coefficients (R2) ranged from 0.46 to 0.63. The average intersubject maximal response relative to the 0.03 Hz condition was 8.0% +/- 1.7% SD occurring at stimulus contrast reversal frequencies between 6 and 15 Hz with an average of 11.8 +/- 3.8 (SD) Hz. From the qualitative and quantitative replication of previous results it is concluded that (10)CO2 PET is a feasible technique for human brain mapping studies and a great improvement compared with the existing oxygen-15-labeled water (H(2)(15)O) PET method, particularly for single subject studies and parametric design.

Brain Mapping↗

Revascularisation of costochondral grafts: an experimental study in domestic pigs.

Mandibular condyles are reconstructed immediately with costochondral grafts (CCGs) in children for several temporomandibular conditions, including ankylosis, benign neoplasia, and chronic arthritis. A prerequisite for growth of CCGs is that they are properly revascularised, but the revascularisation process has not to our knowledge so far been examined. The aim of the present study was therefore to investigate the revascularisation of CCGs when they were used for immediate reconstruction of the mandibular condyle in juvenile domestic pigs. Eleven mandibular condyles were experimentally resected and immediately reconstructed with CCGs. Microangiograms with an Indian ink solution were done 2, 4, 8, and 12 weeks after the reconstructions. The density of vessels was higher in measurement zones facing soft tissues than in those facing mandibular bone at all time points. Revascularisation of the growth plate originated from the surrounding recipient soft tissues and not from an endosteal blood supply from the host mandible ramus.

Animals↗

What do patients, their relatives and medical staff know about genetic therapy?

OBJECTIVES: To investigate the knowledge of, and attitudes towards gene therapy of cancer patients, their relatives, and the staff treating the patients. DESIGN: Cross sectional questionnaire study. SUBJECTS: a) One hundred patients with ovarian cancer either 1) in current treatment with chemotherapy, or 2) in follow up after chemotherapy. b) The relatives accompanying these patients to clinic. c) Fifty doctors and fifty nurses at the hospital in question. MAIN OUTCOME MEASURES: Knowledge about genes and gene therapy, attitudes toward gene therapy and its introduction in the NHS, willingness to accept additional side-effects for a given-therapeutic gain. RESULTS: Patients and relatives have only limited knowledge about genes and gene therapy, but knowledge is also limited about how chemotherapy works. The attitude towards gene therapy is positive, and the worry about gene therapy being like 'playing God' is accepted by less than 10%. There is a strong belief that if gene therapy is effective it should be paid by the NHS (over 85% agree with this).

Attitude of Health Personnel↗

Massive loss of sulfur in HIV infection.

Skeletal muscle tissue from SIV-infected macaques was previously found to contain abnormally high sulfate and low glutathione levels indicative of an excessive cysteine catabolism. We now confirm the peripheral tissue as a site of massive cysteine catabolism in HIV infection and have determined the urinary loss of sulfur per time unit. The comparison of the sulfate concentrations of the arterial and venous blood from the lower extremities of 16 symptomatic HIV+ patients and 18 HIV- control subjects (study 1) revealed (1) that the peripheral tissue of HIV+ patients with or without highly active antiretroviral therapy (HAART) releases large amounts of sulfate and (2) that plasma sulfate, thioredoxin, and interleukin-6 levels are elevated in these patients. A complementary investigation of 64 asymptomatic HIV+ patients and 65 HIV- subjects (study 2) revealed increased plasma sulfate levels in the asymptomatic patients. The analysis of the daily urinary excretion of sulfate and urea of another group of 19 HIV+ patients and 22 healthy HIV- subjects (study 3) confirmed (1) that HIV+ patients experience a massive loss of sulfur and (2) that this loss is not ameliorated by HAART. The sulfur loss of asymptomatic patients was equivalent to a mean loss of about 10 g of cysteine per day. If extrapolated, this would correspond to an alarming negative balance of approximately 2 kg of cysteine per year under the assumption that the normal sulfate excretion equivalent to approximately 3 g of cysteine per day is balanced by a standard Western diet. The abnormally high sulfate/urea ratio suggests that this process drains largely the glutathione pool.

Adult↗

Cortical cerebral metabolism correlates with MRI lesion load and cognitive dysfunction in MS.

OBJECTIVE: To study the association between the cortical cerebral metabolic rate of glucose (CMRglc), MRI T2-weighted total lesion area (TLA), cognitive dysfunction, and neurologic disability in MS. BACKGROUND: MRI lesion load is widely used in the clinical evaluation of the MS patient but little is known about the associated changes in cortical activation. METHODS: Twenty-three patients with clinically definite MS underwent measurements of CMRglc, TLA, motor evoked potentials (MEPs), and cognitive and neurologic disability. CMRglc was calculated using PET and 18-F-deoxyglucose and compared with nine normal control subjects. RESULTS: Reductions in CMRglc (p < 0.01) were found in the cortical global and regional lobar measurements. Furthermore, regional CMRglc (rCMRglc) was reduced in the dorsolateral prefrontal cortex, orbitofrontal cortex, caudate, putamen, thalamus, and hippocampus. Global cortical CMRglc correlated with TLA (Spearman rank correlation coefficient [SRCC] = -0.66, p = 0.001), and rCMRglc correlated with regional lesion load in all cerebral lobes (p < or = 0.05). Global cortical CMRglc and cognitive disability also correlated (SRCC = 0.58, p = 0.015), and stepwise regression analysis showed a significant association between rCMRglc of the right thalamus and cognitive performance as well as TLA. There was no correlation between CMRglc and neurologic disability (Expanded Disability Status Scale) or MEP. CONCLUSION: Global and regional cortical CMRglc is reduced significantly in MS patients compared with normal control subjects. Furthermore, the CMRglc reductions correlate with TLA as well as with cognitive dysfunction, which indicates that MRI white matter lesion burden has a deteriorating effect on cortical cerebral neural function.

Adult↗

Regional differences in the CBF and BOLD responses to hypercapnia: a combined PET and fMRI study.

Previous fMRI studies of the cerebrovascular response to hypercapnia have shown signal change in cerebral gray matter, but not in white matter. Therefore, the objective of the present study was to compare (15)O PET and T *(2)-weighted MRI during a hypercapnic challenge. The measurements were performed under similar conditions of hypercapnia, which were induced by inhalation of 5 or 7% CO(2). The baseline rCBF values were 65.1 ml hg(-1) min(-1) for temporal gray matter and 28.7 ml hg(-1) min(-1) for white matter. By linear regression, the increases in rCBF during hypercapnia were 23.0 and 7. 2 ml hg(-1) min(-1) kPa(-1) for gray and white matter. The signal changes were 6.9 and 1.9% for the FLASH sequence and were 3.8 and 1. 7% for the EPI sequence at comparable echo times. The regional differences in percentage signal change were significantly reduced when normalized by regional flow values. A deconvolution analysis is introduced to model the relation between fMRI signal and end-expiratory CO(2) level. Temporal parameters, such as mean transit time, were derived from this analysis and suggested a slower response in white matter than in gray matter regions. It was concluded that the differences in the magnitude of the fMRI response can largely be attributed to differences in flow and that there is a considerable difference in the time course of the response between gray and white matter.

Adult↗

Use of fluorine-18 fluorodeoxyglucose positron emission tomography in the detection of silent metastases from malignant melanoma.

Correct staging is crucial for the management and prognosis of patients with malignant melanoma. The aim of this prospective study was to compare staging by whole-body positron emission tomography using fluorine-18 fluorodeoxyglucose (18F-FDG) with staging by conventional methods. Thirty-eight patients with malignant melanoma of clinical stage II (local recurrence, in-transit and regional lymph node metastases) or III (metastases to other sites than in stage II) were included in the study. The results of the PET scans were compared with those obtained by clinical examination, computed tomography, ultrasound, radiography, and liver function tests and histology or clinical follow-up. With 18F-FDG PET we found for all foci a sensitivity of 97% and a specificity of 56%, compared with 62% and 22%, respectively, when using routine methods. For intra-abdominal foci, the sensitivity and specificity were 100% for both 18F-FDG PET and routine methods. Corresponding figures for pulmonary/intrathoracic foci were 100% and 33%, respectively. Of the patients included in this study, 34% would not have been staged correctly by conventional methods alone. We conclude from this study that 18F-FDG PET is a sensitive method superior to conventional methods for detecting widespread metastases from malignant melanoma. Mutilating surgery of no benefit can thereby be avoided. 18F-FDG PET is useful as a supplement to clinical examination in melanoma staging.

Female↗

Lateral sinus thrombosis after untreated otitis media. A clinical problem--again?

Antimicrobial agents have greatly reduced the incidence of intracranial complications of infections of the middle ear and mastoid. Too many prescriptions and overconsumption of antibiotics when otitis media is suspected has caused resistance to many antibiotics, leading to a pronounced and justifiable desire to reduce the widespread excessive use of antibiotics. The possible untoward consequences of a too restricted antibiotic policy, however, is illustrated by the following case of a 14-year-old boy who, after non-treatment of an ear infection, fell ill with one-sided headache and vomiting caused by a lateral sinus thrombosis. After intravenous treatment with antibiotics, anticoagulants and ventilation of the middle ear, the infection was cured without complications. This case calls attention to the symptoms of otitic complications arising outside the temporal bone. The physician must always bear in mind the possibility of an unusual event. The general treatment of endocranial complications is outlined, giving details of the treatment given in this special case. We stress that one should not be too cautious in prescribing antibiotics in otitis media.

Adolescent↗

Comparative report on transplantation and relevant ethical problems in five European countries, and some reflections on Japan.

Comparison of transplantation medicine in Sweden, Denmark, Germany, Spain and Portugal reveals many and important differences with respect to frequency of transplantations, frequency of life donations, legal regulations and influence of the family on organ donation. The differences observed are at least partly related to cultural and value differences between the various countries, but many questions need to be studied systematically and in more detail before useful conclusions can be drawn. One study would have to address the problem of how differences in the family influence on organ donation can be explained. Another question needing further clarification concerns the exact meaning of "medical decision" and "medical criteria" because these terms, on which access to- and selection from the waiting list largely depends, are equivocally defined and seem to differ according to different traditions. Open questions also arise with respect to the influence of "closeness or distance" on medical decision making. The findings indicate that it would be premature to propose common guidelines to be observed within Europe as long as the above mentioned and some further questions have not been systematically studied and thoroughly analyzed.

Adult↗

Exposure of the porcine spine to mechanical compression: differences in injury pattern between adolescents and adults.

Recent studies of the spine in adolescents who have sustained trauma have shown injuries to the growth zone, whereas injuries to the vertebral body have been described in other studies of only adults. There are also reports on different clinical signs and radiological findings in adolescents with lumbar disc herniation when compared to adults. In order to find an explanation for these differences between adolescents and adults, this experimental study was performed. Six cadaveric lumbar motion segments (vertebral body-disc-vertebral body) obtained from three young male pigs and six lumbar motion segments obtained from three mature male pigs were tested in axial compression to failure. All units were examined with plain radiography and magnetic resonance imaging before and after compression. After the compression, histological samples were taken from the injury site. In the adolescents, a fracture was consistently found in the endplate through the posterior part of the growth zone, displacing the anulus fibrosus with a bony fragment at the point of insertion to the vertebra. This type of injury could not be detected in any of the adults; instead, there was a fracture of the vertebra in four cases, and in two cases, a rupture of the anulus fibrosus without a bony fragment was seen. This study showed that, when compressed to failure, the weakest part of the lumbar spine of the adolescent pig differs from that of the mature pig in the same way that studies on human spinal units have shown.

Age Factors↗

Decomposition of acoustic fields in quantised Bessel beams

Bessel beams are non-diffracting solutions to the wave equation, which become limited diffraction beams when implemented on finite apertures. In previous work we have applied Fourier-Bessel theory to deduce theoretically that the quantization of the Bessel beam profile on annular arrays results in a field which is a sum of limited diffraction fields. Here we demonstrate this for a five-ring, 20-mm diameter, 2.5-MHz transducer. The quantized field comprises a weighted sum of a main component corresponding to the desired field, along with three other major components and 28 lesser components representing undesired field components. The three major components correspond to limited diffraction beams with narrower beamwidths and shorter depths of field than the desired beam, and we show that these account for most of the discrepancies between the desired field and actual quantized field. An estimate and an interpretation of the number of field components as a function of the wavenumber are also given.

Journal Article↗

Experience in qualitative and quantitative FDG PET in follow-up of patients with suspected recurrence from head and neck cancer.

We evaluated positron emission tomography (PET) with 2-[fluorine-18]fluoro-2-deoxy-D-glucose (FDG) in the detection of recurrent head and neck cancer, and compared visual and quantitative interpretation of PET images for their accuracy in the identification of tumour recurrence. Sixty-two FDG PET studies were performed in 56 patients having a total of 81 lesions, which were clinically suspected for recurrent carcinoma of the head and neck. The PET images were interpreted visually, and tracer uptake was quantitated as the standardised uptake value adjusted to body weight (SUV). Sensitivity of visual interpretation of the PET images for the presence of malignancy ranged from 84 to 95%, and specificity from 84 to 93%, respectively, depending on the selected scheme for grading of the lesions. Malignant lesions accumulated significantly more FDG than the benign ones (the median SUVs were 6.8 and 3.3, respectively, P<0.001). However, there was a wide overlap of the FDG uptake values between these two groups. Hence, the highest accuracy of quantitative analysis in correct identification of tumour recurrence (75% at Receiver Operating Curve analysis) was inferior to that of visual analysis (89%). FDG PET is feasible for the detection of recurrent head and neck cancer. Although quantitation of FDG uptake using SUV shows significantly higher tracer concentrations for malignant than benign lesions, the wide overlap of individual SUVs between these two groups is a serious concern in diagnostic evaluation. Therefore, in clinical practice it may be preferable to identify the presence of tumour recurrence within this patient group by qualitative interpretation of the PET images.

Adult↗