[The Grauballe man. Medical examinations of a conserved moss man's corpse].
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Biomedical subjects
Publications and source records attributed to E S Hansen.
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STUDY DESIGN: A review of the smoking habits in 426 patients who had been followed prospectively for 2 years after a lumbar spinal fusion procedure was conducted. OBJECTIVE: To analyze the effect of pre- and postoperative smoking on clinical and functional outcome after lumbar spinal fusion. SUMMARY OF BACKGROUND DATA: Several animal models have shown a negative effect of nicotine on spinal fusion. At this writing, the clinical effect of nicotine on spinal fusion has not been fully clarified. METHODS: The study comprised 426 patients who underwent lumbar spinal fusion between 1993 and 1997. These patients received a mailed questionnaire regarding their tobacco consumption before and after their surgery. All other data, including preoperative clinical and functional status, were collected prospectively during a 2-year follow-up period. To assess functional outcome, the Dallas Pain Questionnaire was used. RESULTS: The questionnaire was answered by 396 patients (93%). Of these patients, 54.5% (20% more than the background population) were smokers before the operation. Smoking of more than 10 cigarettes daily before the operation and attempted fusion at two or more levels increased the risk of nonunion: odds ratio, 2.01 (P < 0.016) and odds ratio, 3.03 (P < 0.001), respectively. Smoking cessation increased fusion rates to near those of nonsmokers. Smoking had no influence on functional outcome, as assessed by the Dallas Pain Questionnaire, but preoperative smoking predicted a negative answer to the question "Would you undergo the same treatment again, now that you know the result?" (odds ratio, 1.65; P < 0.054). CONCLUSIONS: Smoking was shown to have a negative effect on fusion and overall patient satisfaction, but no measurable influence on the functional outcome as assessed by the Dallas Pain Questionnaire.
OBJECTIVE: To evaluate and compare the diagnostic accuracy of magnetic resonance imaging (MRI), transvaginal ultrasonography (TVS), hysterosonographic examination (HSE), and hysteroscopy in the evaluation of the uterine cavity. DESIGN: Independent double-blind study. SETTING: University medical hospital. PATIENT(S): One hundred six consecutive premenopausal women who underwent hysterectomy for benign diseases. INTERVENTION(S): Results of MRI, TVS, HSE, and hysteroscopy were compared with the results of histopathologic examination at hysterectomy (the gold standard). RESULT(S): The overall sensitivity was MRI 0.76, TVS 0.69, HSE 0.83, and hysteroscopy 0.84. The specificity was MRI 0.92, TVS 0.83, HSE 0.90, and hysteroscopy 0.88 (MRI, HSE, hysteroscopy vs. TVS <0.05). Polyps were missed in 9 of 12 cases at MRI, 7 at TVS, 4 at HSE, and 2 at hysteroscopy (MRI vs. hysteroscopy, and TVS vs. hysteroscopy <0.05). The sensitivity for identification of submucous myomas was MRI 1.0, TVS 0.83, HSE 0.90, and hysteroscopy 0.82; the specificity was MRI 0.91, TVS 0.90, HSE 0.89, and hysteroscopy 0.87 (MRI vs. TVS, and MRI vs. hysteroscopy). Magnetic resonance imaging was significantly more precise than TVS, HSE, and hysteroscopy in determining submucous myoma in-growth (2-way ANOVA <0.05). CONCLUSION(S): For exclusion of abnormalities in the uterine cavity, MRI, HSE, and hysteroscopy were equally effective and slightly superior to TVS. Magnetic resonance imaging and TVS missed endometrial abnormalities such as polyps, but MRI and HSE were most accurate for the evaluation of submucous myomas, and MRI was superior in evaluation of exact submucous myoma in-growth.
OBJECTIVE: To compare the diagnostic potential of magnetic resonance imaging (MRI) and transvaginal ultrasonography (TVS) in the diagnosis of adenomyosis. DESIGN: Double blind set-up. SETTING: University medical school. PATIENT(S): We studied 106 consecutive premenopausal women who underwent hysterectomy for benign reasons. INTERVENTION(S): Transvaginal ultrasonography and MRI were compared with histopathologic examination as the golden standard. MAIN OUTCOME MEASURE(S): Adenomyosis. RESULT(S): Twenty-two (21%) patients had adenomyosis. The sensitivity and specificity were as follows: sensitivity: MRI 0.70 (0.46-0.87) and TVS 0.68 (0.44-0.86) (P=.66); specificity: MRI 0.86 (0.76-0.93) and TVS 0.65 (0.50-0.77) (P=.03). The combination of MRI and TVS was most sensitive (0.89 [0.64-0.98]), but produced the lowest specificity (0.60 [0.44-0.73]). Adenomyosis was not detected by either MRI or TVS at uterine volumes >400 mL. Exclusion of uteri >400 mL from the analysis improved the diagnostic precision of MRI, but not that of TVS. The diagnostic accuracy at MRI was improved by calculating the maximum difference between the thinnest and thickest junctional zone (JZdif) (i.e., > or =5-7 mm). CONCLUSION(S): Magnetic resonance imaging was superior to TVS for the diagnosis of adenomyosis. Magnetic resonance imaging had a higher specificity than TVS, but their sensitivities were in line. The diagnostic accuracy of MRI, as that of TVS, was at an intermediate level, but the diagnostic accuracy of the former improved by exclusion of uteri >400 mL. The combination of MRI and TVS produced the highest level of accuracy for exclusion of adenomyosis, but the low specificity may necessitate further investigation of positive findings. Measurement of the difference in junctional zone thickness may optimize the diagnosis of adenomyosis at MRI.
Many pathological bone conditions are accompanied by changes in bone perfusion. However, no method has yet allowed investigation of vascular reactivity in human bone tissue. In the present study, arterial segments (diameter approximately 0.25 mm) were isolated from human bone biopsies and mounted as ring preparations in vitro. The viability of the arteries and the effects of adrenoceptor stimulations were investigated. Combined alpha- and beta-adrenoceptor stimulation (noradrenaline 10(-8)-10(-5) M) and specific alpha1-adrenoceptor stimulation (phenylephrine, 10(-8)-10(-4.5) M) induced concentration-dependent contractions in all arteries. Selective stimulation of alpha2-receptors (B-HT 933, 10(-8)-10(-3.5) M) only induced contraction in three of eight arteries. Stimulation of beta-receptors with isoprenaline (10(-6) M) resulted in vasorelaxation in 3 of 10 arteries. In all arteries, acetylcholine (10(-10)-10(-5) M) induced vasorelaxation, demonstrating preserved function of the endothelium. The results suggest that primarily alpha1-receptors are responsible for adrenoceptor induced vasoconstriction in human bone while functional alpha2- and beta-receptors may not be consistently expressed. The model is the first to allow investigations on vascular reactivity in human bone tissue and may become valuable for assessment of both normal and pathological bone physiology.
Information is sparse concerning the effect of oophorectomy (OOX) on bone vascularization and blood flow of possible significance for altered remodeling. Whether OOX affects functional characteristics of isolated bone resistance arteries was investigated. Ring preparations (diameter approximately 250 microm) of small femoral bone arteries from oophorectomized and sham-operated rabbits were mounted on a myograph six weeks postoperatively. Cumulative concentration response curves were obtained for various agonists at a normalized lumen diameter. Oophorectomy did not significantly influence lumen diameter, maximal response to high potassium, or maximal response to high potassium and 10(-5) M noradrenaline. However, OOX significantly increased the maximal response to noradrenaline (OOX 2.14 +/- 0.36 N/m, Sham 1.25 +/- 0.14 N/m) and endothelin-1 (OOX 1.76 +/- 0.32, Sham 0.95 +/- 0.15) in metaphyseal arteries. Moreover, the corresponding maximal active pressure for the agonists was significantly increased. OOX did not influence endothelial function assessed by the effects of acetylcholine or substance P. The functional responses of diaphyseal arteries were unaffected by OOX. The study demonstrates regional differences in the effects of OOX on small arteries of importance for control of vascular resistance in bone which suggests a relation between altered vascular function after ovarian hormonal withdrawal and the changes in bone turnover associated with osteoporosis.
In a prospective randomized study, we evaluated the risk of lumbar posterolateral spinal fusion at an unintended level due to bone graft migration. 130 patients underwent fusion supplemented by pedicle screw fixation (Cotrell-Dubousset, 64 patients) or uninstrumented fusion (66 patients). This was assessed by two independent observers on antero-posterior, and lateral radiographs taken 1 year after surgery. All patients had ben operated on at the preoperatively planned levels. Both observers agreed that fusion had taken place at an unintended level in 19 cases (14%). We found a tendency towards a higher risk of this "complication" when using supplementary pedicle screw fixation. The functional outcome, assessed by the Dallas Pain Questionnaire and the Low Back Pain Rating scale, was similar in patients having fusion at an unintended level and in patients fused only at the intended levels. There was no difference between the two groups concerning reoperation rates, postoperative smoking or social status. We conclude that unintended fusion occurs and tends to be commoner with the use of pedicle screw instrumentation. However, this complication seems not to affect the functional outcome if fusion has taken place at the intended level.
Treatment with corticosteroids is a risk factor for non-traumatic avascular necrosis of the femoral head, but the pathological mechanism is poorly understood. Short-term treatment with high doses of methylprednisolone is used in severe neurotrauma and after kidney and heart transplantation. We investigated the effect of such treatment on the pattern of perfusion of the femoral head and of bone in general in the pig. We allocated 15 immature pigs to treatment with high-dose methylprednisolone (20 mg/kg per day intramuscularly for three days, followed by 10 mg/kg intramuscularly for a further 11 days) and 15 to a control group. Perfusion of the systematically subdivided femoral head, proximal femur, acetabulum, humerus, and soft tissues was determined by the microsphere technique. Blood flow in bone was severely reduced in the steroid-treated group. The reduction of flow affected all the segments and the entire epiphysis of the femoral head. No changes in flow were found in non-osseous tissue. Short-term treatment with high-dose methylprednisolone causes reduction of osseous blood flow which may be the pathogenetic factor in the early stage of steroid-induced osteonecrosis.
STUDY DESIGN: Bone mineral density and regional blood flow were measured in pigs during long-term methylprednisolone treatment. OBJECTIVES: To investigate possible changes in bone mineral density and vertebral blood flow during long-term glucocorticoid treatment. SUMMARY OF BACKGROUND DATA: Steroid-induced vertebral osteonecrosis preferentially involves endplates and adjacent cancellous bone. The precise etiology of vertebral osteonecrosis during long-term glucocorticoid treatment is unknown. METHODS: Twenty-four 10-week-old female Danish landrace sister pigs from 12 litters were treated in two groups. Twelve animals received oral methylprednisolone for 3 months at a daily dose of 100 mg. The 12 sister pigs received no steroid treatment and served as controls. Regional blood blow was measured by means of microspheres in predefined regions of the C6, T11, and L6 vertebrae. In vitro DEXA scanning of the L2-L4 vertebra was performed to assess bone mineral density. RESULTS: Vertebral cancellous bone and endplate regional blood flow were decreased in the C6 and L6 vertebrae among corticosteroid-treated pigs compared with that of controls.- Width-adjusted lumbar vertebral bone mineral density (g/cm3) was unchanged, whereas projectional lumbar vertebral bone mineral density (g/cm2) was decreased in corticosteroid-treated pigs. CONCLUSIONS: Long-term methylprednisolone treatment decreases vertebral bone blood flow mainly in cancellous bone and endplates. This may be an important factor in the pathogenesis of osteonecrosis secondary to glucocorticoid treatment. Lumbar vertebral bone mineral density was unchanged in growing pigs on long-term glucocorticoid treatment when expressed as volumetric bone density. The effect of glucocorticoid treatment on vertebral bone mineral density appears to depend on whether it is expressed as projectional (g/cm2) or volumetric bone mineral density (g/cm3). Vertebral and longbone growth was reduced during methylprednisolone treatment.
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Stresses are environmental factors which restrict growth or cause a potentially adverse change in an organism. The exposure of developing organisms to environmental stresses may have several physiological consequences including a decrease in immunocompetence. However, mounting an immune response against a foreign antigen may in itself constitute a cost for developing organisms. This cost has potentially long-term consequences for adult function and fitness. This study examines the growth and developmental stability of Japanese quail++ chicks challenged by three non-pathogenic antigens: sheep red blood cells, which assess T-cell-dependent immune responses, and Mycoplasma synoviae and Newcastle disease virus, which assess T-cell-independent responses. Increases in both body mass and wing length were significantly reduced in antigen-challenged birds compared to control birds. Fluctuating asymmetry (FA) in the masses of primary feathers increased from the innermost (1) to the outermost (10) position on the wing. In addition, antigen challenge by M. synoviae and sheep red blood cells was associated with an increase in FA. The cell-mediated response measured by reaction to phytohaemagglutinin was significantly depressed in M. synoviae-challenged birds. White blood cell counts, except for monocytes, were elevated in response to all three antigen treatments. Total plasma protein and haematocrit also differed between treatments but exhibited no clear relationship to antigen challenge. Immune responses clearly impose a stress on developing chicks. Additional research will be required to determine the long-term consequences of developmental stress and assess the selective forces that influence the strength of the immune responses of chicks.
The aim was to evaluate the effect of supplementary pedicle screw fixation (Cotrel-Dubousset [CD]) in posterolateral lumbar spinal fusion. The study comprises 130 patients undergoing lumbar or lumbosacral fusion for spondyloisthesis grades I-II or degenerative segmental instability conditions. The patients were randomly allocated for no instrumentation (n = 66) or CD instrumentation (n = 64) in posterolateral lumbar fusion. A 97.7% follow-up was achieved. There were no significant differences between the two groups concerning fusion rates assessed by X-ray or functional outcomes assessed by Dallas Pain Questionnaire. The global patient satisfaction was 82% in the instrumented group versus 74% in the noninstrumented group. Instrumentation increased both operation time, blood loss, and early re-operation rates significantly. A high patient satisfaction was found in both groups. However, the results from this study do not justify the general use of pedicle screw fixation alone as an adjunct to posterolateral lumbar fusion.
The capacity of the individual patient to initiate osteoblast proliferation as a predictor for successful lumbar spinal fusion has not yet been reported. The objectives of this study were, first, to analyze the relationship between in vitro osteoblast proliferation and clinical bony fusion in the individual patient in order to predict the fusion outcome and, second, to measure the effect of preoperative tobacco smoking on osteoblast proliferation. Sixty-one patients (mean age 46 years) underwent posterolateral lumbar fusion in the period 1994-1995. Thirty-eight patients received CD pedicle screw implants and 23 received posterolateral fusions alone. During surgery, autogenous iliac bone was harvested and 1 g of trabecular bone without blood or bone marrow was then isolated for cell culturing. The cultures were classified as excellent (confluence within 4 weeks), good (confluence between 4 and 6 weeks) and poor (no or poor growth). Spine fusion was evaluated by two independent observers from plain anterior-posterior, lateral, and flexion/extension radiographs taken 1 year postoperatively, and the functional outcome was measured by the Dallas Pain Questionnaire (DPQ). Twenty-three patients had excellent, 19 good, and 19 poor in vitro osteoblast proliferation. Bony fusion was obtained in 77% of patients: 83% in the CD instrumentation group and 70% in the non-instrumentation group (NS). There was no significant correlation between osteoblast proliferation and spinal fusion or functional outcomes when analyzing the CD instrumentation and non-instrumentation groups together or separately. Elderly patients had a significantly poorer osteoblast proliferation than younger patients (P < 0.008). Preoperative tobacco consumption had no discernible effect on osteoblast proliferation, and no correlation between smoking and fusion was found. Further refinement of autologous osteoblast culturing may provide a biological tool for selection of patients who require biological enhancement of their bone fusion capacity. The poorer osteoblast proliferation related to advanced age supports the important negative biological influence of age on bony fusion. However, with more sensitive testing and better discrimination, other results are possible - or can in any event not be excluded.
The study presented here is a pilot study in five patients with unstable thoracolumbar spine fractures treated with transpedicular OP-1 transplantation, short segment instrumentation and posterolateral fusion. Recombinant bone morphogenetic protein-7 in combination with a collagen carrier, also referred to as OP-1, has demonstrated ability to induce healing in long-bone segmental defects in dogs, rabbits and monkeys and to induce successful posterolateral spinal fusion in dogs without need for autogenous bone graft. Furthermore OP-1 has been demonstrated to be effective as a bone graft substitute when performing the PLIF maneuver in a sheep model. Five patients with single-level unstable burst fracture and no neurological impairment were treated with intracorporal OP-1 transplantation, posterior fixation (USS) and posterolateral fusion. One patient with osteomalacia and an L2 burst fracture had an additional intracorporal transplantation performed proximal to the instrumented segment, i.e. OP-1 into T 12 and autogenous bone into T 11. Follow-up time was 12-18 months. On serial radiographs, Cobb and kyphotic angles, as well as anterior, middle and posterior column heights, were measured. Serial CT scans were performed to determine the bone mineral density at fracture level. In one case, radiographic and CT evaluation after 3 and 6 months showed severe resorption at the site of transplantation, but after 12 months, new bone had started to fill in at the area of resorption. In all cases there was loss of correction with regard to anterior and middle column height and sagittal balance at the latest follow-up. These preliminary results regarding OP-1 as a bone graft substitute and stimulator of new bone formation have been disappointing, as the OP-1 device in this study was not capable of inducing an early sufficient structural bone support. There are indications to suggest that OP-1 application to a fracture site in humans might result in detrimental enhanced bone resorption as a primary event.
OBJECTIVE: To study the penetration of group B streptococcus (GBS) through human chorioamniotic membranes in vitro. STUDY DESIGN: Chorioamniotic membranes from seventeen healthy women were mounted onto glass cylinders and placed in tissue culture trays constituting a two-compartment system with a maternal compartment internally and a fetal compartment externally. GBS from healthy pregnant women and from newborn babies with sepsis were added to the maternal compartment at densities from 10(7) to 10(9) colony forming units (cfu) per ml. RESULTS: Irrespective of inoculum density, GBS was not recovered from the fetal compartment within a 20 h incubation period. By histology, micro-colonies of GBS were found on the maternal surface after 8 h, but invasion of the morphologically intact membranes was not observed. A five log reduction in cfu occurred in the maternal compartment with amnion when GBS were suspended in saline. CONCLUSION: In this in vitro model the membranes appear to constitute an effective barrier against ascending infection.
BACKGROUND: To examine the mortality pattern of Danish doctors for the period 1973-1992. METHODS: A historical prospective cohort study based on the membership register of the Danish Medical Association. The study population consisted of 21,943 medical doctors, 6012 of whom were women. The doctors' cause-specific mortality was compared with that of the general population. RESULTS: The study covered about 277,000 person-years. A total of 2387 deaths occurred from 1 January 1973 to 31 December 1992. The doctors' mortality was lower than that of the general population. Both sexes showed a standardized mortality ratio (SMR) below one for cancer, circulatory diseases and other natural causes. Mortality due to lung cancer was particularly low. The SMR for suicide was significantly increased, 1.6 for males (95% CI: 1.4-1.9) and 1.7 for females (95% CI: 1.1-2.5). The suicide rate was increased, in particular because of an increased number of suicides by poisoning. In addition female doctors displayed a relatively high mortality due to accidents and other types of violent death. CONCLUSIONS: Compared with the general population the doctors' mortality was low, but the mortality from external causes was increased, mainly due to an excess number of suicides.
BACKGROUND: Enkephalins are opioid peptides that can modulate immune responses and inflammatory processes. Furthermore, they inhibit keratinocyte proliferation/differentiation in vitro. Previously, we have shown that enkephalins are present in increased amounts in lesional psoriasis. OBJECTIVE: To determine the effect of topical treatment with the vitamin D analogue calcipotriol and the corticosteroid mometasone furoate on the level of methionine-enkephalin (enk) in psoriatic lesions. METHODS: Twelve psoriatic patients were treated with calcipotriol and mometasone furoate for 14 days without or with hydrocolloid occlusion. Keratome biopsies were obtained from treated and untreated skin, and the extracted enk was quantified by radioimmunoassay. Furthermore, punch biopsies were obtained for immunohistochemical analysis. RESULTS: Clinically, both calcipotriol and mometasone furoate improved psoriasis to the same degree, the effects being more pronounced after occlusion. Histologically, treatment with mometasone furoate without occlusion decreased both the epidermal thickness/parakeratosis and the number of dermal immunocompetent cells (CD3- and CD68-positive cells). In contrast, treatment with calcipotriol without occlusion reduced the epidermal thickness and the degree of parakeratosis but decreased the number of CD3- and CD68-positive cells only slightly. The mean enk level was decreased by 26 and 86% by calcipotriol without and with occlusion and by 16 and 63% by mometasone furoate without and with occlusion, respectively. The decreases in the enk levels corresponded to the degree of clinical improvement but not to the histological changes. CONCLUSION: The increased levels of enk in psoriatic lesions are reduced in parallel with the clinical improvement induced by a topical vitamin D analogue and a corticosteroid. Because enkephalins can modulate epidermal differentiation and inflammatory processes, the findings indicate that enkephalins may play a role in the pathogenesis of psoriasis.