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Biomedical subjects

S Hansen

Publications and source records attributed to S Hansen.

At least 37 records · Page 2Linked to original sources

Chalcone derivatives antagonize interactions between the human oncoprotein MDM2 and p53.

The oncoprotein MDM2 inhibits the tumor suppressor protein p53 by binding to the p53 transactivation domain. The p53 gene is inactivated in many human tumors either by mutations or by binding to oncogenic proteins. In some tumors, such as soft tissue sarcomas, overexpression of MDM2 inactivates an otherwise intact p53, disabling the genome integrity checkpoint and allowing cell cycle progression of defective cells. Disruption of the MDM2/p53 interaction leads to increased p53 levels and restored p53 transcriptional activity, indicating restoration of the genome integrity check and therapeutic potential for MDM2/p53 binding antagonists. Here, we show by multidimensional NMR spectroscopy that chalcones (1,3-diphenyl-2-propen-1-ones) are MDM2 inhibitors that bind to a subsite of the p53 binding cleft of human MDM2. Biochemical experiments showed that these compounds can disrupt the MDM2/p53 protein complex, releasing p53 from both the p53/MDM2 and DNA-bound p53/MDM2 complexes. These results thus offer a starting basis for structure-based drug design of cancer therapeutics.

Antineoplastic Agents↗

Molecular characterisation of two novel maize LRR receptor-like kinases, which belong to the SERK gene family.

Genes encoding two novel members of the leucine-rich repeat receptor-like kinase (LRR-RLK) superfamily have been isolated from maize (Zea mays L.). These genes have been named ZmSERK1 and ZmSERK2 since features such as a putative leucine zipper (ZIP) and five leucine rich repeats in the extracellular domain, a proline-rich region (SPP) just upstream of the transmembrane domain and a C-terminal extension (C) after the kinase domain identify them as members of the SERK (somatic embryogenesis receptor-like kinase) family. ZmSERK1 and ZmSERK2 are single-copy genes and show 79% identity among each other in their nucleotide sequences. They share a conserved intron/exon structure with other members of the SERK family. In the maize genome, ZmSERK1 maps to position 76.9 on chromosome arm 10L and ZmSERK2 to position 143.5 on chromosome arm 5L, in regions generally not involved in duplications. ZmSERK1 is preferentially expressed in male and female reproductive tissues with strongest expression in microspores. In contrast, ZmSERK2 expression is relatively uniform in all tissues investigated. Both genes are expressed in embryogenic and non-embryogenic callus cultures.

Amino Acid Sequence↗

No effect of the cortisol-synthesis inhibitor metyrapone on alcohol drinking: a pilot study.

Two bases for this study were the theory of stress as a provoking factor for high alcohol consumption in human being and findings that the stress hormones stimulate ethanol intake in rats. We therefore investigated whether the cortisol-synthesis inhibitor metyrapone could reduce high alcohol consumption in socially stable subjects who reported drinking mainly for relaxation purposes. Most of the investigated subjects were found to be alcohol dependent (81%), with moderately high levels of intake, yet they had not reported more severe life problems. All subjects reported their daily alcohol consumption during 2-week baseline, medication, and postmedication periods. Sixteen subjects were given 1 g of metyrapone orally daily for 14 days, and 15 subjects received placebo. Morning serum cortisol concentration was assessed four times in the course of the study period. Metyrapone treatment was not found to reduce alcohol consumption more than placebo. Serum cortisol concentrations remained within the laboratory reference interval during the study and did not differ between the study groups. In this study, we found that a cortisol-synthesis inhibitor had no effect on alcohol consumption. One reason may be that cortisol secretion has no role in the maintenance of high alcohol consumption. On the other hand, because this study is the first of its kind, further studies using other doses of treatment and treatment schedules are suggested.

Adult↗

A deficit in attentional set-shifting of violent offenders.

BACKGROUND: Recent brain imaging studies suggest that proneness to violence and antisocial behaviour may be associated with dysfunction of the prefrontal cortex. The present study. therefore, examined aspects of prefrontally guided executive functions in a group of criminal violent men. METHODS: Violent offenders undergoing forensic psychiatric examination by court order undertook computerized tasks for planning, visual working memory and attentional set-shifting from the Cambridge Neuropsychological Test Automated Battery. Their performance was compared to that of subjects with marginal mental retardation and normal controls. RESULTS: Violent offenders performed well on tasks for spatial and figurative working memory, as well as on a test for planning. A marked impairment was observed in the attentional set-shifting task: offenders made significantly more errors than the other groups when required to shift attention from one perceptual dimension to another. Reversal learning was also deficient. Correlational analyses within the offender group revealed that poor performance on the perceptual shift problem was associated with fewer errors in tasks for working memory and planning. CONCLUSIONS: The present results suggest that violent offenders show dual impairments in inhibitory cognitive control. First, they are deficient in shifting attention from one category to another. Secondly, the ability to alter behaviour in response to fluctuations in the emotional significance of stimuli is compromised. These deficits might constitute cognitive reflections of the biological prefrontal alterations observed in this group of people.

Adolescent↗

Rapid subcutaneous IgG replacement therapy at home for pregnant immunodeficient women.

The use of slow or rapid, subcutaneous, IgG (SCIG) infusions in pregnant women with primary antibody deficiencies has been described earlier, though only in single-case reports. In this study, we have evaluated the effect of rapid, SCIG infusions during 11 pregnancies in nine women [six women with common variable immunodeficiency (CVID), two with IgG-subclass deficiencies, and one with combined IgA and IgG2 deficiency]. The weekly infusions were given by the women themselves at a dose of 100 mg/kg/week throughout the pregnancy. No adverse systemic reactions or pronounced, local tissue reactions were recorded during or after the more than 400 infusions. The 11 babies were healthy and were born after 38-42 weeks of uneventful gestation. The concentrations of maternal S-IgG at the time of delivery in the four women with CVID ranged from 6.0 to 8.3 g/L, with cord/maternal S-IgG ratios of 1.0-1.5. The IgG subclasses were transferred to the infants. The SCIG home-therapy regime was greatly appreciated by the women.

Adult↗

The effect of short-term strength training on human skeletal muscle: the importance of physiologically elevated hormone levels.

The effect of strength training and endogenously elevated hormone levels (plasma testosterone, growth hormone (GH) and cortisol) was studied in 16 young untrained males, divided into an arm only training group, A, and a leg plus arm training group, LA, in order to increase circulating levels of anabolic hormones. Both groups performed the same one-sided arm training for 9 weeks, twice a week. Group A trained only one arm (AT), the contralateral arm serving as control (AC), whereas group LA additionally trained their legs following the training of the one arm (LAT), with the contralateral arm serving as control (LAC). In spite of the attempt to match the two groups, the initial isometric arm strength was 20-25% lower for group LA compared to group A (significant for the arm to be trained). Isometric strength increased significantly in LAT and LAC by 37% and 10%, respectively, while the 9% and 2% increases in AT and AC, respectively, remained insignificant. Isokinetic strength increased at one out of three velocities tested for the trained arm relative to the untrained arm in both group A and group LA (P<0.05). Functional strength increased significantly by 20% in LAT, 18% in LAC, 19% in AT, and 17% in AC. Hormonal responses were monitored during the first and last training sessions. Resting hormone levels remained unchanged for both groups. However, during the first training session plasma testosterone as well as plasma cortisol increased significantly in group LA but not in group A. Plasma GH rose in all exercise tests, except during the last test in group LA, but was significantly higher in group LA than in group A in the first training session. In conclusion, a larger relative increase in isometric strength was found in the group having the highest hormonal response. However, due to the initial difference in isometric strength caution must be taken with the interpretation of this finding, which may only indicate a possible link between anabolic hormones and muscle strength with training.

Adult↗

Characterization and quantification of mouse mannan-binding lectins (MBL-A and MBL-C) and study of acute phase responses.

Rat monoclonal antibodies (MoAbs) against mouse mannan-binding lectin (MBL)-A and MBL-C were generated and assays for MBL-A and MBL-C were constructed. This allowed for the quantitative analysis of both proteins for the first time. Previously only MBL-A has been quantified using less standardized methods. In a mouse serum pool the concentrations were now determined at 7.5 microg MBL-A and 45 microg MBL-C per ml. On gel permeation chromatography of mouse serum, MBL-A eluted corresponding to a M(r) of 850 kDa whereas the majority of MBL-C eluted corresponding to a Mr of 950 kDa. On sucrose density gradient centrifugation the sedimentation velocities of MBL-A and MBL-C were estimated at 7.3 S and 10.8 S, respectively. The MBL-A and MBL-C levels in 10 laboratory mice strains were compared and found to vary between 4 microg/ml to 12 microg/ml, and 16 microg/ml to 118 microg/ml, respectively. After the induction of acute phase responses by intraperitoneal injection of either casein or lipopolysaccharide (LPS), MBL-A was found to increase approximately two-fold, with a maximum after 32 h, while MBL-C did not increase significantly. In comparison, serum amyloid A component (SAA) peaked at 15 h with an approximate 100-fold increase.

Acute-Phase Proteins↗

Predictors of medical events and of their competitive interactions in the Cardiac Insufficiency Bisoprolol Study 2 (CIBIS-2).

AIMS: Predictive factors for medical events and interactions between events were not reported in the Cardiac Insufficiency Bisoprolol Study 2 (CIBIS-2). We examined the interactions among death, permanent treatment withdrawals, nonlethal cardiovascular hospitalizations and their own occurrence in a given patient, the treatment received, and baseline variables during CIBIS-2. METHODS AND RESULTS: A Cox model for censored data was used to analyze the relations among baseline variables, medical events, and their interactions with treatment. We used competitive risk analysis to examine the interactions between successive events in a given patient during follow-up. No baseline variable predicted the reduction of mortality with bisoprolol. Withdrawal from bisoprolol therapy was more frequent in patients whose baseline heart rate was in the lower tertile of the distribution (P =.0002) but otherwise was not different between patients randomized to bisoprolol and to placebo. Event history analysis revealed that bisoprolol reduced mortality (P =.0006) and hospitalizations for nonlethal cardiovascular events (P =.003) in patients in whom treatment was not permanently withdrawn. Analysis of survival curves in patients who permanently discontinued treatment showed that bisoprolol did not reduce mortality compared with placebo in this population (relative risk 1.03, 95% CI 0.67-1.59; P =.88). Recurrent nonlethal events were reduced by bisoprolol. CONCLUSION: In CIBIS-2, medical events were significantly influenced by treatment withdrawal. Patients who derive benefit from bisoprolol therapy are those in whom treatment is not permanently withdrawn.

Adrenergic beta-Antagonists↗

Bacterial contamination associated with electronic faucets: a new risk for healthcare facilities.

OBJECTIVE: To investigate the safety of the hospital water supply following a major flood. DESIGN: Surveillance was conducted of the hospital water supply as it entered the hospital and at randomly selected water faucets throughout the facility. SETTING: A newly constructed surgical critical-care unit in a 265-bed community hospital that had to be evacuated and was out of operation for 6 weeks following a major flood of the city. METHODS: Random water samples throughout the facility were analyzed for heterotrophic plate counts (HPCs), chlorine, and coliforms utilizing standard methods. RESULTS: Water samples entering the hospital met appropriate standards, indicating the city water distribution system was not contaminated. Of 169 faucets tested, 13 (22%) of 59 electronic faucets exceeded the HPC threshold, and 12 (11%) of 110 manual faucets exceeded the HPC threshold (P<.14). A comparison of two brands of electronic faucets with manual faucets and with each other revealed that the HPC threshold was exceeded by 11 (32%) of 34 brand A faucets as compared to 12 (11%) of 110 manual faucets (P<.006). The HPC threshold was exceeded by 2 (8%) of 25 brand B faucets compared to 12 (11%) of 110 manual faucets (P<.94). Contamination rates of brand A and brand B faucets differed significantly (P<.003). Similar testing 2 months after hyperchlorination of the water supply indicated that the HPC threshold was exceeded by 16 (52%) of 31 brand A faucets compared to 10 (9.%) of 110 manual faucets (P<.0000003) and by 2 (18%) of 25 brand B faucets compared to 10 (9%) of 110 manual faucets (P=1.0). CONCLUSIONS: A certain brand of electronic water faucet used in the hospital was associated with unacceptable levels of microbial growth in water and was a continuing source of bacteria potentially hazardous to patients.

Chlorine↗

The maize MADS box gene ZmMADS3 affects node number and spikelet development and is co-expressed with ZmMADS1 during flower development, in egg cells, and early embryogenesis.

MADS box genes represent a large gene family of transcription factors with essential functions during flower development and organ differentiation processes in plants. Addressing the question of whether MADS box genes are involved in the regulation of the fertilization process and early embryo development, we have isolated two novel MADS box cDNAs, ZmMADS1 and ZmMADS3, from cDNA libraries of maize (Zea mays) pollen and egg cells, respectively. The latter gene is allelic to ZAP1. Transcripts of both genes are detectable in egg cells and in in vivo zygotes of maize. ZmMADS1 is additionally expressed in synergids and in central and antipodal cells. During early somatic embryogenesis, ZmMADS1 expression is restricted to cells with the capacity to form somatic embryos, and to globular embryos at later stages. ZmMADS3 is detectable only by more sensitive reverse transcriptase-PCR analyses, but is likewise expressed in embryogenic cultures. Both genes are not expressed in nonembryogenic suspension cultures and in isolated immature and mature zygotic embryos. During flower development, ZmMADS1 and ZmMADS3 are co-expressed in all ear spikelet organ primordia at intermediate stages. Among vegetative tissues, ZmMADS3 is expressed in stem nodes and displays a gradient with highest expression in the uppermost node. Transgenic maize plants ectopically expressing ZmMADS3 are reduced in height due to a reduced number of nodes. Reduction of seed set and male sterility were observed in the plants. The latter was due to absence of anthers. Putative functions of the genes during reproductive and vegetative developmental processes are discussed.

Amino Acid Sequence↗

Characterisation of breathing and associated central autonomic dysfunction in the Rett disorder.

AIM: To investigate breathing rhythm and brain stem autonomic control in patients with Rett disorder. SETTING: Two university teaching hospitals in the United Kingdom and the Rett Centre, Sweden. PATIENTS: 56 female patients with Rett disorder, aged 2-35 years; 11 controls aged 5-28 years. DESIGN: One hour recordings of breathing movement, blood pressure, ECG R-R interval, heart rate, transcutaneous blood gases, cardiac vagal tone, and cardiac sensitivity to baroreflex measured on-line with synchronous EEG and video. Breathing rhythms were analysed in 47 cases. RESULTS: Respiratory rhythm was normal during sleep and abnormal in the waking state. Forced and apneustic breathing were prominent among 5-10 year olds, and Valsalva breathing in the over 18 year olds, who were also most likely to breathe normally. Inadequate breathing peaked among 10-18 year olds. Inadequate and exaggerated breathing was associated with vacant spells. Resting cardiac vagal tone and cardiac sensitivity to baroreflex were reduced. CONCLUSIONS: Labile respiratory rhythms and poor integrative inhibition in Rett disorder suggest brain immaturity. Linking this to an early monoaminergic defect suggests possible targets for the MECP2 gene in clinical intervention. Exaggerated and inadequate autonomic responses may contribute to sudden death.

Adolescent↗

An epidemiological study of the relations between exposure to organophosphate pesticides and indices of chronic peripheral neuropathy and neuropsychological abnormalities in sheep farmers and dippers.

OBJECTIVES: To investigate the hypothesis that chronic low level exposure to organophosphates (OPs) in sheep dips is related to clinically detectable measures of polyneuropathy. METHODS: The design was a cross sectional exposure-response study of sheep dippers and other non-exposed groups. The study group consisted of 612 sheep dipping farmers, 53 farmers with no sheep dipping experience, and 107 ceramics workers. Retrospective exposure information was obtained by questionnaire based on stable and easily identifiable features of sheep dipping found during the first phase of the study; in particular, estimates of handling concentrate and splashing with dilute dip. Neurological assessments were based on a standard neuropathy symptoms questionnaire, and thermal and vibration quantitative sensory tests. RESULTS: Adjusted for confounders there was a weak positive association between cumulative exposure to OPs and neurological symptoms, the significance of which was dependent on the inclusion of a few individual workers with extremely high exposure. There was no evidence of an association between cumulative exposure and the thermal or vibration sensory thresholds. However, separating the effects of exposure intensity and duration showed a higher prevalence of symptoms, primarily of a sensory type, among sheep dippers who handled the OP concentrate. There was also evidence that sensory and vibration thresholds were higher among concentrate handlers, the highest exposed group of dippers. CONCLUSIONS: The findings showed a strong association between exposure to OP concentrate and neurological symptoms, but a less consistent association with sensory thresholds. There was only weak evidence of a chronic effect of low dose cumulative exposure to OPs. It is suggested that long term health effects may occur in at least some sheep dippers exposed to OPs over a working life, although the mechanisms are unclear.

Adolescent↗

Synchronization of lower limb motor unit activity during walking in human subjects.

Synchronization of motor unit activity was investigated during treadmill walking (speed: 3-4 km/h) in 25 healthy human subjects. Recordings were made by pairs of wire electrodes inserted into the tibialis anterior (TA) muscle and by pairs of surface electrodes placed over this muscle and a number of other lower limb muscles (soleus, gastrocnemius lateralis, gastrocnemius medialis, biceps femoris, vastus lateralis, and vastus medialis). Short-lasting synchronization (average duration: 9.6 +/- 1.1 ms) was observed between spike trains generated from multiunit electromyographic (EMG) signals recorded by the wire electrodes in TA in eight of nine subjects. Synchronization with a slightly longer duration (12.8 +/- 1.2 ms) was also found in 13 of 14 subjects for paired TA surface EMG recordings. The duration and size of this synchronization was within the same range as that observed during tonic dorsiflexion in sitting subjects. There was no relationship between the amount of synchronization and the speed of walking. Synchronization was also observed for pairs of surface EMG recordings from different ankle plantarflexors (soleus, medial gastrocnemius, and lateral gastrocnemius) and knee extensors (vastus lateralis and medialis of quadriceps), but not or rarely for paired recordings from ankle and knee muscles. The data demonstrate that human motor units within a muscle as well as synergistic muscles acting on the same joint receive a common synaptic drive during human gait. It is speculated that the common drive responsible for the motor unit synchronization during gait may be similar to that responsible for short-term synchronization during tonic voluntary contraction.

Adult↗

Increased alcohol intake and behavioral disinhibition in rats with ventral striatal neuron loss.

A previous study of ours reported excessive alcohol intake, enhanced defensive aggressiveness (hyperreactivity towards the experimenter), impulsive behavior, and reduced cortical serotonin levels in rats following extensive basal forebrain axon-sparing lesions involving the septal area and the ventral striatum. This constellation of signs resembles that seen clinically in "Dionysian" alcoholics. The present investigation aimed at examining the effect of ibotenic acid lesions restricted to the septal area or the ventral striatum on this behavioral profile. Experiment 1 indicated that medium-sized lesions (induced by infusing 0.35 microl ibotenic acid in each hemisphere) encompassing the septal area or the ventral striatum elicited a qualitatively similar behavioral profile. Both lesion types markedly enhanced the intake of 6% ethanol, and both groups were significantly more hyperreactive towards the experimenter. A brief doorbell signal elicited significantly more fleeing in rats with basal forebrain lesions, and licking from an electrified waterspout in the punished drinking test caused lesser suppression of locomotor activity than normal. Both groups also showed significant deficits in food hoarding. Histological examination revealed that the posterior portion of the ventral striatal lesion typically overlapped with the anterior portion of the septal lesion. Experiment 2 avoided this neuropathological overlap, and examined groups bearing small discrete lesions (induced by infusing 0.15 microl ibotenic acid in each hemisphere) restricted to either the accumbens part of the ventral striatum or the dorsal septal area. Lesions to the nucleus accumbens were associated with an increase in home-cage alcohol drinking, no hyperreactivity towards the experimenter, potentiation of fleeing at the expense of freezing in response to a sudden auditory signal, and disinhibited behavior in the punished drinking test with increased punished responding and reduced behavioral suppression. Rats with small septal lesions showed a weak enhancement of defensive aggression, but no other behavioral alterations. Our results suggest that ventral striatal neuron loss gives rise to excessive alcohol drinking and enhanced impulsivity.

Acoustic Stimulation↗

Purification and characterization of two mannan-binding lectins from mouse serum.

Mannan-binding lectin (MBL) is a serum protein that activates the complement system after binding to glycoconjugates found on the surface of microorganisms. By molecular cloning two forms of MBL have been identified in the mouse (mMBL-A and mMBL-C), but only mMBL-A has been purified and characterized at the protein level. MBL-C has been termed the liver form of MBL. The present report describes the purification and characterization of mMBL-A and mMBL-C from serum. The two forms of mMBL could be separated both by ion-exchange and carbohydrate-affinity chromatography. The initial identification by immunochemical technique was confirmed by N-terminal amino-acid sequencing. Both proteins give bands corresponding to polypeptide chains of 28 kDa on SDS-PAGE in the reduced state, but mMBL-A migrated more rapidly than mMBL-C in acid/urea-PAGE, in accordance with the calculated pIs. Both forms mediated activation of complement component C4 in mannan-coated microtiter wells. MBL-A showed a higher affinity for d -glucose and alpha-methyl-d -glucose then did MBL-C. Serum concentrations of mMBL-A in laboratory strains and wild mice were found to vary from 5 to 80 microg/ml, with wild mice tending to show higher levels than laboratory strains.

Amino Acid Sequence↗

Are heart transplant recipients more likely to develop skin cancer than kidney transplant recipients?

Non-melanoma skin cancer is frequent in organ transplant recipients. The risk of posttransplant cutaneous squamous cell carcinoma in Norwegian heart transplant recipients (n = 148) and kidney transplant recipients (n = 1020) on triple immunosuppressive therapy with cyclosporine, azathioprine, and prednisolone, transplanted between 1983 and 1992, were studied. After adjustment for age at transplantation in multivariable Cox models, heart transplant recipients had a significantly 2.8-times higher risk of developing squamous cell carcinoma relative to kidney transplant recipients. The risk relative to the general population (standardized incidence ratio) was higher in heart transplant recipients than in kidney transplant recipients. The results indicate that heart transplant recipients are more likely to be diagnosed with skin cancer than kidney transplant recipients, probably due to the higher doses of cyclosporine and azathioprine after heart transplantation used at our center in the study period.

Azathioprine↗

The homologue of mannose-binding lectin in the carp family Cyprinidae is expressed at high level in spleen, and the deduced primary structure predicts affinity for galactose.

Mannose-binding lectin (MBL) participates in the innate immune system as an activator of the complement system and as an opsonin after binding to certain carbohydrate structures on microorganisms. We isolated and characterized cDNA transcripts encoding an MBL homologue from three members of the carp family Cyprinidae, the zebrafish Danio rerio, the goldfish Carassius auratus, and the carp Cyprinus carpio. The carp and zebrafish transcripts contain two polyadenylation sites and RT-PCR on mRNA from carp tissues revealed the carp transcript to be most prominently expressed in the spleen. The deduced mature proteins contain 228 or 233 amino acids with a short N-terminal segment containing a single conserved cysteine expected to form interchain disulfide bridges, a collagen domain interrupted by four amino acids between two glycine residues, a neck region predicted to form an alpha-helical coiled-coil structure, and a C-terminal carbohydrate recognition domain (CRD). Several of the structurally important residues in the CRD are conserved, but the residues known to interact with the calcium ion and hydroxyl groups of the carbohydrate ligand are different. The amino acid motif EPN, important for mannose specificity, was QPD in the Cyprinidae homologue, suggesting specificity for galactose instead. The identity between the deduced amino acid sequences is more than 90% between the carp and the goldfish and 68% and 65% between these two species, respectively, and the zebrafish. The identity with bird and mammalian MBLs ranges from 28 to 33%.

Amino Acid Sequence↗

Sagittal alignment in lumbosacral fusion: relations between radiological parameters and pain.

The objective of this study was to conduct a radiological analysis of posture before and after lumbosacral fusion to evaluate the influence of spinal alignment on the occurrence and pattern of post surgical pain. The study included 81 patients, of whom 51 had a history of previous low back surgery. We excluded patients with suspected or confirmed nonunion. In the fusion group, the 27 patients who were pain free after the procedure were compared to the 54 patients with residual pain. Thirty patients had pain only or primarily when they were standing immobile, 18 when they were sitting immobile, and six in both positions. Measurements were done on full-length lateral radiographs of the spine, with the patient standing according to Duval Beaupère criteria. The subgroup with postfusion pain was characterized at baseline by a more vertical sacrum with less sacral tilt (ST) (P < 0.0062) and more pelvic tilt (PT) (P < 0.0160). PT at last follow-up (PT fu) correlated with the presence of postfusion pain (NP: P = 0.0003). In the patients with postfusion pain, PT was almost twice the normal value. ST at last follow-up (ST fu) in the standing position was also correlated with the presence of postfusion pain (P < 0.0001) indicating that the sacrum remained abnormally vertical in the subjects with postfusion pain. Using logistic regression, the only prognostic factor for residual pain at last follow-up was ST fu. Both at pre-operative evaluation and at last follow-up, patients with pain in the standing position or in both the standing and sitting positions were characterized at pre-operative status by a more vertical sacrum with less sacral tilt. The results of this study indicate that, achieving a strong fusion should not be the only goal. Appropriate position of the fused vertebrae is also of paramount importance to minimize muscle work during posture maintenance. The main risk is failing to correct or to causing excessive pelvic retroversion with a vertical sacrum leading to a sagittal alignment that replicates the sitting position. This situation is often accompanied by loss of lumbar lordosis and adversely affects stiff or degenerative hips.

Adult↗