Biomedical subjects
Publications and source records attributed to S Hansen.
An unusual case of vertical atlantoaxial dislocation without medulla oblongata or spinal cord injury is reported. The pathogenic process suggested occipito-axial dislocation. The case was treated surgically with excellent results on mobility and pain.
The present article analyzed the dramatic increase in alcohol ingestion that is known to occur in laboratory rats subjected to food restriction. In the first experiment, we wished to know when during the day food restricted animals consume the "extra" alcohol ration. Determinations of ethanol drinking at 3-h intervals throughout the day revealed that although food-restricted animals drink much ethanol at all times of the day, they retain a definite daily rhythm such that peak intake occurs during the dark hours. The second experiment tested the hypothesis that chronic food restriction is accompanied by positive alliesthesia for the taste of alcohol. To answer this question, we employed the taste reactivity method to measure hedonic and aversive reactions to 6% ethanol as a function of nutritional status. It was found that two weeks of food restriction, which approximately doubled the voluntary intake of ethanol, was associated with a significant increase in the hedonic response elicited by intraoral infusions of ethanol. Alcohol also elicited fewer aversive responses in food restricted subjects. Because chronic food restriction increases adrenal corticosterone secretion, we used the corticosterone synthesis inhibitor metyrapone as a tool to assess the importance of adrenal corticosterone secretion for the increased palatability of alcohol observed during food restriction. The third experiment demonstrated that attenuation of corticosterone synthesis significantly reduced the hedonic taste reactions to alcohol observed in food-restricted rats; this drop in alcohol taste reward was accompanied by a nonsignificant increase in the aversive reaction to alcohol. The final experiment investigated the effect of prolonged exposure to exogenous corticosterone on the taste reactivity to ethanol in freely fed subjects. Adrenalectomized animals bearing corticosterone implants for 3 weeks found the taste of alcohol more pleasant than did intact or adrenalectomized rats implanted with blank pellets. Taken together, the present results suggest that food restriction is associated with an apparent increase in the sensory reward--positive alliesthesia--derived from alcohol; this effect appears to be mediated by increased adrenal corticosterone secretion.
Research on alcoholism have identified a subgroup in which the drinking problem is associated with high rates of violence, an impulsive disposition and signs of reduced serotonin functioning in the brain. The present study reports that male Wistar rats with ibotenic acid-induced (5 micrograms/0.5 microliter) neuron loss in the basal forebrain (ventral striatum, septal area and adjacent structures) showed behavioral and neurochemical signs not unlike this subtype of alcoholics. Thus, rats with this lesion exhibited excessive 6% alcohol drinking in a two-bottle choice test and showed augmentation of certain defensive behaviors, including defensive aggression and increased activity-during signal. In the punished drinking test, a passive avoidance task which taps psychological mechanisms underlying impulsivity [56], experimental rats were not different from sham-operated controls with regard to the number of punished licks, but punishment evoked less disruption of ongoing behavior in subjects with basal forebrain damage. The virtual absence of food hoarding in the face of normal feeding may constitute yet another sign of increased impulsivity, indicating as it does a diminished influence of future rewards on behavior. As expected, in view of ibotenic acid's selectivity for neuronal perikarya, the concentrations of dopamine, serotonin and norepinephrine were normal in the lesioned area. However, the levels of serotonin and norepinephrine in the cortex were reduced. A separate experiment examined the extent to which serotonin depletion alone reproduced the behavioral profile induced by basal forebrain neuron loss. However, measures of alcohol consumption, defensive behavior and impulsivity were not different from controls in rats given intracerebroventricular 5,7-DHT (150 micrograms/20 microliters), except for a modest increase in defensive aggression.
BACKGROUND: Nonmelanoma skin cancer occurs frequently in organ transplant recipients, but the relative importance of different immunosuppressive therapy regimens is unclear. OBJECTIVE: We studied the risk of skin cancer in the complete, single-center Norwegian cohort of kidney and heart transplant recipients (n = 2561). METHODS: We determined cancer risk estimation by means of standardized incidence ratios and multivariate Cox regression. RESULTS: Transplant recipients had an increased risk of cutaneous squamous cell carcinoma (SCC) (65-fold), malignant melanoma (3-fold), and Kaposi's sarcoma (84-fold), and of lip SCC (20-fold), compared with the general population. After adjustment for age, kidney transplant recipients receiving cyclosporine, azathioprine, and prednisolone had a significantly (2.8 times) higher risk of cutaneous SCC relative to those receiving azathioprine and prednisolone. After adjustment for age and type of immunosuppressive regimen, heart transplant recipients had a significantly (2.9 times) higher risk than kidney transplant recipients. CONCLUSION: The risk of cutaneous SCC, malignant melanoma, Kaposi's sarcoma, and lip SCC is increased in kidney and heart transplant recipients. The risk of posttransplant cutaneous SCC is related to the degree of immunosuppression caused by long-term immunosuppressive therapy.
BACKGROUND: Helicobacter pylori infection is an established risk factor for gastric adenocarcinoma. Potential confounding by socioeconomic factors has not been adequately assessed, and the magnitude of the relative risk in relation to gastric subsites, morphologic subtypes, sex, age, and follow-up time need further study. METHODS: We conducted a serologic case-control study nested within the Norwegian JANUS cohort. Between 1972 and 1986 serum was collected from 101,601 subjects who were followed up with regard to cancer development through 1992. RESULTS: Among 208 gastric adenocarcinoma cases, we found a strong positive association between H. pylori infection and non-cardia gastric cancer (odds ratio (OR), 5.15; 95% confidence interval (CI), 2.83-9.37), and a statistically significant negative association with cardia cancer (OR, 0.40; 95% CI, 0.20-0.77). Adjustment for socioeconomic factors and smoking did not materially alter the effect estimates. The association between the infection and non-cardia cancer was stronger for tumors distal to the angulus and tended to be stronger in women than in men. The results were similar across Laurén morphologic subtypes. CONCLUSIONS: These results strengthen the evidence of H. pylori infection as a risk factor in non-cardia gastric cancer. A negative association with H. pylori infection was found for cardia cancer.
UNLABELLED: The intrathecal injection of 0.7-1 mg/kg meperidine provides spinal anesthesia of only short duration. In this study, we investigated the effects of three different doses of meperidine for spinal anesthesia on the duration and level of sensory block and the incidence of side effects. Forty-five African men were randomly allocated to receive one of three doses of intrathecal meperidine: Group A = 1.2 mg/kg, Group B = 1.5 mg/kg, and Group C = 1.8 mg/kg. The duration of sensory block was significantly longer after 1.5 mg/kg compared with 1.2 mg/kg meperidine (112 +/- 19 vs 79 +/- 27 min; P = 0.001). Increasing the dose to 1.8 mg/kg did not further increase the duration of block. The level and the onset of the block were not affected by the dose. Common side effects were fatigue (27%), pruritus (20%), and nausea (7%). Seven patients had respiratory depression and seven had a decrease of systolic arterial blood pressure (SAP) >30% from baseline. There was no difference in the incidence of any side effect among groups. Respiratory depression and decreases in SAP were observed 5-50 min after meperidine injection. Twenty-two patients had no pain after the sensory block had terminated. We conclude that increasing the dose of meperidine from 1.2 to 1.5 mg/kg increased the duration, but not the level, of sensory block without an increase in side effects. IMPLICATIONS: Intrathecal meperidine 1 mg/kg provides surgical anesthesia for only 40-90 min. We investigated the effects of three larger doses of meperidine in 45 African men. The 1.5 and 1.8 mg/kg doses provide a longer duration of anesthesia compared with 1.2 mg/kg. Nausea, pruritus, and respiratory depression were common in all dose groups. We conclude that increasing the dose of meperidine from 1.2 to 1.5 mg/kg increased the duration, but not the level, of sensory block without an increase in side effects.
Seventy patients met our inclusion criteria in this retrospective study, all with an arthroscopic/arthrotomic-verified isolated total anterior cruciate ligament (ACL)-rupture and a minimum follow-up period of 3 years and no associated lesions. Due to emigration/death, 3 patients were not available for follow-up. Of the remaining 67, 25 patients underwent secondary ACL-reconstruction, equivalent to a failure rate of the initial non-operative treatment of 37%. All patients were initially treated conservatively. This left 42 patients for follow-up--9 answered a questionnare and 33 went through follow-up examination after a median of 7.1 years (range 3.3 14.6) including IKDC-evaluation form, Lysholm & Tegner score, ES-SKA-score, clinical examination and Stryker Laxity test. In the present study all values represent the 33 patients available for follow-up. Soccer, handball and alpine skiing were most frequently responsible for the injury. We observed in the 33 patients a decline in median Lysholm score from 100 (90-100) pretraumatic to 86 (42-100) at follow-up, and a decrease in median Tegner values from 7 (3-9) pretraumatic to 5 (2-7) at follow-up. All but 2 patients demonstrated a decline in Lysholm score, and only 3 patients returned to their preinjury level. According to the ESSKA-classification, the number of "cutting-sports performers" declined dramatically from 24 to 2. All but one patient ascribed their decline in activity to their knee status. The Stryker-measured AP-translocations were significantly higher on the injured knee (7.27) compared to the healthy knee (4.80) (P < 0.05). Intermittant rest pain was suffered by 63% of the patients. During the time from inclusion until follow-up, 13 (39%) patients sustained an additional ipsilateral knee lesion, most commonly a tear of the medial meniscus. The overall outcome was expressed in a low frequency of return to unrestricted preinjury level of function, and a high level of instability complaints resulting in many secondary ACL-reconstructions. Naturally some have adapted to their ultimate functional disability, but only through modification of activities, and the overall outcome after conservative therapy of these ACL-ruptures was not satisfactory.
Rapid changes in heart rate are caused by changes in parasympathetic tone. The NeuroScope is an electronic device designed to offer an objective real-time measure of instantaneous cardiac vagal tone by phase demodulation of a high-resolution time domain of R-R wave intervals. Data are displayed against an arbitrary but linear scale, the cardiac index of parasympathetic activity (CIPA). To validate this method, 10 conscious healthy dogs were each given six incremental doses of atropine (0.01 mg/kg) to a total dose of 0.06 mg/kg or equal volumes of saline. A dose-response curve was constructed. At the maximum dose of atropine, CIPA values fell to 1. 3 +/- 0.7% (SD) of baseline, whereas R-R intervals fell to 51.5 +/- 11.5% of baseline, and standard deviation of the R-R wave interval fell to 10.6 +/- 6.5% of baseline. These findings show that the NeuroScope can provide a specific real-time index of cardiac vagal tone in dogs without need for recourse to atropine.
Intraoperative ultrasonography (IOUS) was used to evaluate the location and compressive effects of intraspinal fragments in thoracolumbar fractures and the efficacy of reduction maneuvers in patients operated on for isolated or attached intraspinal fragments or for global posterior wall disruption. Dynamic IOUS was used to evaluate the effects of traction and lordosis. Fifty-eight patients were evaluated using a 7.5 MHz ultrasound probe, including 27 treated by impaction, 19 by removal of apparently isolated fragments, and 12 by traction followed by lordosis for global posterior wall disruption. IOUS had limitations and problems caused by split fragments and residual pedicular attachments that can compromise intraoperative maneuvers. The risk of secondary displacement of isolated fragments treated by impaction was very high. In particular, the pinching effect produced by T-shaped fractures was commonly responsible for secondary displacement. IOUS evaluation of canal clearance after fragment removal was satisfactory, but did not provide quantitative data. IOUS was easier to perform and apparently more reliable than intraoperative myelography. The dynamic IOUS data suggest that, except for severely tilted fragments that are completely free or remain attached to a pedicle, residual discal attachments significantly influence the likelihood of successful reduction.
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The protein surface is the interface through which a protein senses the external world. Its composition of charged, polar and hydrophobic residues is crucial for the stability and activity of the protein. The charge state of seven of the twenty naturally occurring amino acids is pH dependent. A total of 95% of all titratable residues are located on the surface of soluble proteins. In evolutionary related families of proteins such residues are particularly prone to substitutions, insertions and deletions. We present here an analysis of the residue composition of 4038 proteins, selected from 125 protein families with < 25% identity between core members of each family. Whereas only 16.8% of the residues were truly buried, 40.7% were > 30% exposed on the surface and the remainder were < 30% exposed. The individual residue types show distinct differences. The data presented provides an important new approach to protein engineering of protein surfaces. Guidelines for the optimization of solvent exposure for a given residue are given. The cutinase family of enzymes has been investigated. The stability of native cutinase has been studied as a function of pH, and has been compared with the cutinase activity towards tributyrin. Whereas the onset of enzymatic activity is linked with the deprotonation of the active site HIS188, destabilization of the 3D structure as determined by differential scanning calorimetry is coupled with the loss of activity at very basic pH values. A modeling investigation of the pH dependence of the electrostatic potentials reveals that the activity range is accompanied by the development of a highly significant negative potential in the active site cleft. The 3D structures of three mutants of the Fusarium solani pisi cutinase have been solved to high resolution using X-ray diffraction analysis. Preliminary X-ray data are presented.
Long-term trends in the incidence, prognosis, and mortality of patients with ovarian cancer and borderline tumours in Norway were examined based on data from the population-based Cancer Registry of Norway. The incidence of ovarian cancer rose continuously from the mid-1950s to the mid-1980s. There was also an increasing trend in the incidence of borderline tumours from the early 1970s to the early 1990s. The prognosis for patients with ovarian cancer has improved since the 1950s. In 1989-93 the five-year relative survival rate was 37%. The prognosis for patients with borderline tumours was very favourable, with a five-year relative survival rate of 93% (1970-93). The mortality from ovarian cancer has been almost constant since the 1960s.
The Scandinavian countries exhibit some of the highest incidence rates of ovarian cancer in the world. Prognosis is poor, and the crude 5-year relative survival was 36% in the Nordic countries in the 1980s. Histology-specific prognostic trends in 5-year relative survival of patients with ovarian cancer and borderline tumours were examined, based on data from the population-based Cancer Registry of Norway. Relative risks (RRs) of dying were derived from Cox regression models. Logistic regression analysis on the proportion of cases with a localised tumour was performed. The 5-year relative survival rate of patients with ovarian cancer increased steadily from 1954 to 1993, being most pronounced in women below the age of 65 at the time of diagnosis. No improvement was seen for women older than 75. For all patients with ovarian cancer, an RR of dying of 0.48 (95% CI = 0.44-0.53) was estimated in 1989-1993 compared with 1954-1958. For patients with epithelial cancer, an RR of 0.63 (95% CI = 0.57-0.69) was seen in 1989-1993 compared with 1970-1973. Patients with mucinous, endometrioid and clear cell tumours had the highest odds of having a localised tumour. The age-adjusted 5-year relative survival rate of patients with borderline tumours was almost constant between 1970 and 1993, at about 93%. The prognosis of patients with ovarian cancer in Norway has improved since the 1950s. The very favourable prognosis of patients with borderline tumours has remained unchanged since the 1970s.
The contribution of each of the structural domains of p53 to its function has been discussed widely in the literature. Crystallographic studies have revealed much about the structure of the core DNA binding domain, but as it has not been possible to use this approach for the intact protein, the effect of the domains flanking the core must be investigated by more indirect techniques. In this study a series of truncated murine p53 proteins has been investigated for DNA binding activity at 4 degrees C and 37 degrees C, transcriptional activation, and tumour suppression activity. Full-length p53, and truncations lacking the N terminus, purified from a baculovirus expression system all show latency for DNA binding; that is, they must be activated to bind by association with a C-terminal antibody such as PAb421. This demonstrates that latency for DNA binding is independent of the N terminus. Truncations lacking the C-terminal oligomerisation domain, and the isolated core domain, can only be activated to bind DNA and PAb1620 (an antibody recognising the wild-type conformation of the core domain) in the presence of cross-linking antibodies, while murine core only binds to DNA in the presence of PAb1620. An analysis of the thermostability of DNA binding revealed that antibodies that bind the N terminus of p53 could protect the protein against loss of activity at 37 degrees C. C-terminal antibodies, however, were ineffective unless the N-terminal 37 amino acid residues were absent. The N terminus may retain some secondary structure, since it is the main contributor to the anomalous migration in SDS-polyacrylamide gels. Our results suggest that the N terminus has a destabilising effect that influences conformation of p53 at 37 degrees C, so cellular proteins binding to the N terminus in vivo may modulate p53 conformation and stability. The effects on thermostability are also direct evidence showing that antibodies binding to N-terminal deletions create a conformational change in the rest of the molecule. In addition, longer deletions of the C terminus reduce the ability of p53 to transactivate target genes and inactivate tumour suppression activity, while truncations of the N terminus retain partial tumour suppression activity. Our results clearly show participation of both the N and C termini in the regulation of all the functions of p53 at 37 degrees C, indicating that distinct, independent domains interact with each other within, the flexible structure of p53.
Intraoperative ultrasonography is recommended for operations on the thoracolumbar spine to complement the information provided by standard X-ray, intensifier screen or myelography. There are no unanimates opinions concerning the impaction or exeresis of these fragments. The aim of this study was to show the advantages of intraoperative ultrasonography for anatomic determination and control of the maneuvers used. This study included 46 cases with fractures from T11 to L2. Ultrasonography was performed during the intraoperative reduction provided by the installation and the pedicular instruments. The authors stress the limits of the anatomic and geographic determination, as well as tilting of the fragments because of the size of the ultrasonographic head. The quality of the exeresis may be falsely interpreted in the presence of fragments with a section of less than 4 mm, lateralized, double fragments or in the presence of massive intraoperative haemorrhage. Analysis of the impaction results is more complicated because all of these fragments displaced themselves secondarily. The ligamentum communis vertebralis posterior has no anatomical containing role. The tilting before the impaction and the state of the overlying intervertebral disk represent essential factors for failures. Ultrasonography is better than intraoperative myelography. Nevertheless, it still needs to be complemented by intraoperative profile X-rays and a very precise preoperative CT scan of the intervertebral disk lesions analysis of complicated cases (fragments with residual pedicular attachments--type A 3.1.2.; T-like fractures--type A 3.2.1.).
This study examined the effect of the benzodiazepine, midazolam, on the consumption and palatability of 6% ethanol in male Wistar rats. In the first experiment, it was found that midazolam (5 mg/kg) increased home cage ethanol drinking 0-2 h after administration. Another intake experiment, in which ethanol was infused directly into the oral cavity through an indwelling catheter, also showed that midazolam (10 mg/kg) stimulated alcohol ingestion. The affective response to intraoral infusions of ethanol (1 ml during 1 min) was subsequently monitored in benzodiazepine-treated rats. Taste reactivity testing showed that midazolam (5-10 mg/kg) significantly increased the occurrence of hedonic orofacial responses and suppressed the number of passive drippings. A similar response pattern was observed following administration of diazepam (5 mg/kg) and chlordiazepoxide (10 mg/kg), but not after exposure to cis(Z)flupentixol (10 mg/kg). Midazolam also increased the incidence of hedonic responses in alcohol-naive rats with no previous access to ethanol in the home cages. Hedonic responsiveness did not appear to diminish with repeated benzodiazepine exposure: the behaviour of rats given five midazolam injections (10 mg/kg every second day) was similar to that shown by rats with no benzodiazepine pre-exposure. The increased hedonic response to ethanol induced by midazolam was blocked by pretreatment with the benzodiazepine receptor antagonist flumazenil (10 mg/kg), the latter drug exerting no effects on its own. The present results suggest that benzodiazepines, by acting on GABA(A) receptors, may facilitate ethanol intake by increasing ethanol's taste hedonic properties.