Quality of life and functional outcomes after transanal total mesorectal excision for rectal cancer-results from the implementation period in Denmark.

BACKGROUND: The standard operation for mid- and low rectal cancer total mesorectal excision (TME) is routinely performed as minimally invasive surgery. TME is associated with temporary or permanent functional impairment of pelvic organs, causing reduced quality of life (QoL). Concerns have been raised that the newest minimally invasive approach, transanal TME (TaTME), may further reduce urogenital and anorectal functions. OBJECTIVE: To determine if functional outcomes affecting QoL are altered after TaTME. Primary end-point is the impact of TaTME on QoL and functional outcomes. Secondary end-point is assessing differences in QoL and functional outcomes after TME surgery from below (TaTME) or above (transabdominal TME). DESIGN, SETTING, AND PARTICIPANTS: Observational study consisting of prospectively registered self-reported questionnaire data collected at baseline and follow-ups after TaTME. All patients who underwent TaTME during the Danish national implementation phase were included. Central surveillance of the implementation included questionnaires concerning QoL and functional outcomes. Analyses of functional results from the Danish cohort of the ROLARR trial (Jayne et al. in JAMA 318:1569-1580, (2017) are reported separately for perspective, representing the transabdominal approach to TME, i.e., laparoscopic- or robotic-assisted TME (LaTME/RoTME). Applied questionnaires include EORTC QLQ-C30, SF-36, LARS, ICIQ-MLUTS, ICIQ-FLUTS, IPSS, IIEF, SVQ, and FSFI. RESULTS: A total of 115 TaTME procedures were registered August 2016 to April 2019. LaTME/RoTME patients (n = 92) were operated on January 2011 to September 2014. A temporary postoperative decrease of QoL (global health status and functional scales) was observed, yet long-term results were unaffected by surgery in both groups. In TaTME patients, the anorectal dysfunction increased significantly (p < 0.001) from preoperative baseline to 13.5 months follow-up, where 67.5% (n = 52) reported major LARS symptoms. Urinary function was not significantly impaired after TME regardless of technique. The paucity of responses concerning sexual function precludes conclusions. CONCLUSIONS: Although an initial reduction in QoL after TME occurs, it normalizes within the first year postoperatively. In concurrence with international results, we found that significant anorectal dysfunction is common after TaTME. No data on anorectal function was available for LaTME/RoTME patients for comparison. We found no indications that transanal TME is inferior to transabdominal TME surgery concerning urogenital functions or health-related QoL.

Gene expression signatures for colorectal cancer microsatellite status and HNPCC.

The majority of microsatellite instable (MSI) colorectal cancers are sporadic, but a subset belongs to the syndrome hereditary non-polyposis colorectal cancer (HNPCC). Microsatellite instability is caused by dysfunction of the mismatch repair (MMR) system that leads to a mutator phenotype, and MSI is correlated to prognosis and response to chemotherapy. Gene expression signatures as predictive markers are being developed for many cancers, and the identification of a signature for MMR deficiency would be of interest both clinically and biologically. To address this issue, we profiled the gene expression of 101 stage II and III colorectal cancers (34 MSI, 67 microsatellite stable (MSS)) using high-density oligonucleotide microarrays. From these data, we constructed a nine-gene signature capable of separating the mismatch repair proficient and deficient tumours. Subsequently, we demonstrated the robustness of the signature by transferring it to a real-time RT-PCR platform. Using this platform, the signature was validated on an independent test set consisting of 47 tumours (10 MSI, 37 MSS), of which 45 were correctly classified. In a second step, we constructed a signature capable of separating MMR-deficient tumours into sporadic MSI and HNPCC cases, and validated this by a mathematical cross-validation approach. The demonstration that this two-step classification approach can identify MSI as well as HNPCC cases merits further gene expression studies to identify prognostic signatures.

Aerobic oxidation of aminoacetone, a threonine catabolite: iron catalysis and coupled iron release from ferritin.

Aminoacetone (AA) is a threonine and glycine catabolite long known to accumulate in cri-du-chat and threoninemia syndromes and, more recently, implicated as a contributing source of methylglyoxal (MG) in diabetes mellitus. Oxidation of AA to MG, NH(4)(+), and H(2)O(2) has been reported to be catalyzed by a copper-dependent semicarbazide sensitive amine oxidase (SSAO) as well as by Cu(II) ions. We here study the mechanism of AA aerobic oxidation, in the presence and absence of iron ions, and coupled to iron release from ferritin. Aminoacetone (1-7 mM) autoxidizes in Chelex-treated phosphate buffer (pH 7.4) to yield stoichiometric amounts of MG and NH(4)(+). Superoxide radical was shown to propagate this reaction as indicated by strong inhibition of oxygen uptake by superoxide dismutase (SOD) (1-50 units/mL; up to 90%) or semicarbazide (0.5-5 mM; up to 80%) and by EPR spin trapping studies with 5,5-dimethyl-1-pyrroline-N-oxide (DMPO), which detected the formation of the DMPO-(*)OH adduct as a decomposition product from the DMPO-O(2)(*)(-) adduct. Accordingly, oxygen uptake by AA is accelerated upon addition of xanthine/xanthine oxidase, a well-known enzymatic source of O(2)(*)(-) radicals. Under Fe(II)EDTA catalysis, SOD (<50 units/mL) had little effect on the oxygen uptake curve or on the EPR spectrum of AA/DMPO, which shows intense signals of the DMPO-(*)OH adduct and of a secondary carbon-centered DMPO adduct, attributable to the AA(*) enoyl radical. In the presence of iron, simultaneous (two) electron transfer from both Fe(II) and AA to O(2), leading directly to H(2)O(2) generation followed by the Fenton reaction is thought to take place. Aminoacetone was also found to induce dose-dependent Fe(II) release from horse spleen ferritin, putatively mediated by both O(2)(*)(-) and AA(*) enoyl radicals, and the co-oxidation of added hemoglobin and myoglobin, which may be viewed as the initial step for potential further iron release. It is thus tempting to propose that AA, accumulated in the blood and other tissues of diabetics, besides being metabolized by SSAO, may release iron and undergo spontaneous and iron-catalyzed oxidation with production of reactive H(2)O(2) and O(2)(*)(-), triggering pathological responses. It is noteworthy that noninsulin-dependent diabetes has been frequently associated with iron overload and oxidative stress.

[Febrile convulsions, Treatment and prognosis]. / Feberkramper. Behandling og prognose.

Epidemiological data indicate that the long-term prognosis in the vast majority of children with febrile seizures is good. Three main problems are important for the treatment: febrile seizures are extremely upsetting for the parents, the recurrence rate is 30-40% and the febrile status occurs unpredictably and is potentially damaging to the CNS. There is universal agreement that daily prophylaxis with valproate, primidone, or phenobarbital should only be used in highly selected cases, if at all. The effectiveness of phenytoin and carbamazepine has not been documented. Antipyretic treatment does not reduce the recurrence rate. Intermittent diazepam prophylaxis at times of fever may or may not reduce the recurrence rate significantly, but there is no data to suggest that it improves the long-term outcome, as compared with short-term seizure control, in terms of IQ, cognition, academic progress, motor control, and subsequent epilepsy. Acute anticonvulsive treatment with rectal diazepam in solution or other benzodiazepines is effective in aborting recurrent seizures with almost the effectiveness of i.v. treatment and is safe, simple, and easy to use for the parents. The long-term prognosis is probably uninfluenced by the type of treatment given in early childhood. It has not been established that acute anticonvulsive treatment with benzodiazepine is better than placebo.

[Tension-free hernioplasty with a plug and a patch. A prospective long-term study of 483 cases of inguinal or femoral hernia]. / Tensionsfri hernioplastik med "plug" og plade. Prospektiv langtidsopgørelse af 483 ingvinal- og femoralhernier.

INTRODUCTION: The aim of this study was to assess the introduction of mesh plug and patch for hernia repair. MATERIALS AND METHODS: A prospective study was carried out on 483 consecutive cases of inguinal or femoral hernia treated at a county hospital in the period November 1993 to April 1997. The final follow-up was done by questionnaire. RESULTS: The operation was performed as a day-in procedure in 59% of the patients, and 35% stayed in the ward overnight. Normal daily activities were resumed within three (2-7) days (median [interquartile range]), and the sick leave was 7 (4-14) days. There were few postoperative complications, and reoperation was done in two cases. The overall recurrence rate was 5%, and for primary hernias 4%. There were no recurrences after operation for femoral hernia. Chronic pain was reported in 17% of the patients, 12% felt pain only during strenuous exercise. The observation at time was 46 (36-56) months (median [interquartile range]). DISCUSSION: Patients operated on with the mesh plug and patch technique had a short hospital stay and a short convalescence. The recurrence rate was acceptable.

[Child abuse and osteogenesis imperfecta. How do we distinguish?]. / Børnemishandling og osteogenesis imperfecta. Hvordan ser vi forskel?

Osteogenesis imperfecta is a hereditary connective tissue disorder. Typical manifestations are fragile bones with multiple bone fractures and bone deformities. A history of minimal or no trauma and recurrent fractures is a feature of OI, but is also typical of non-accidental injury (NAI). OI and NAI are relevant differential diagnoses when a child presents with unexplained fractures. The differential diagnostic problems are reviewed, all of which are important for the child both in terms of treatment and for prognosis, socially and medicolegally. We conclude that comprehensive clinical evaluation is adequate for differential diagnosis and that both OI and NAI can be diagnosed by positive anamnestic and objective signs. Mild OI IV without other signs than fracture(s) is very rare and the new entity temporary brittle bone disease is hypothetical; the diagnosis of these two clinical pictures is unacceptable in small children. Routine analysis of collagens should not be performed.

Chemiluminescent aldehyde and beta-diketone reactions promoted by peroxynitrite.

Peroxynitrite is shown here to promote the aerobic oxidation of isobutanal (IBAL) and 3-methyl-2,4-pentanedione (MP) in a pH 7.2 phosphate buffer into acetone plus formate and biacetyl plus acetate, respectively. These products are expected from dioxetane intermediates, whose thermolysis is known to be chemiluminescent (CL). Accordingly, the extent of total oxygen uptake by IBAL at different concentrations parallels the corresponding CL maximum intensities. The pH profile based on oxygen uptake data for the MP reaction matches the titration curve of peroxynitrous acid (pK(a) approximately 7), indicating that peroxynitrite anion is the oxidizing agent. Energy transfer studies with IBAL and the 9, 10-dibromoanthracene-2-sulfonate ion, a triplet carbonyl detector, indicates that triplet acetone (tau = 19 micros) is the energy donor. It is postulated that IBAL- or MP-generated triplet carbonyls are produced by the thermolysis of dioxetane intermediates, which are formed by the cyclization of alpha-hydroperoxide intermediates produced by insertion of dioxygen into the IBAL or MP enolyl radicals, followed by their reduction. Accordingly, EPR spin-trapping studies with 3,5-dibromo-4-nitrosobenzenesulfonic acid (DBNBS) and 2-methyl-2-nitrosopropane (MNP) revealed the intermediacy of carbon-centered radicals, as expected for one-electron abstraction from the enol forms of IBAL or MP by peroxynitrite. The EPR data obtained with IBAL also reveal formation of the isopropyl radical produced by competitive nucleophilic addition of ONOO(-) to IBAL, followed by homolytic cleavage of this adduct and beta-scission of the resulting Me(2)CHCH(O(-))O(*). Superstoichiometric formation of fragmentation products from IBAL or MP attests to the prevalence of an autoxidation chain reaction, here proposed to be initiated by one-electron abstraction by ONOO(-) from the substrate. This work reveals the potential role of peroxynitrite as a generator of electronically excited species that may contribute to deleterious and pathological processes associated with excessive nitric oxide and aldehyde production.

Febrile seizures: treatment and prognosis.

Recent epidemiologic data indicate that the vast majority of children with febrile seizures have a normal longterm outcome. A precise knowledge of the short- and long-term outcome with or without treatment, and short- and long-term side effects is an important prerequisite for assessing the various treatment strategies. We focus on the impact of short-term or prophylactic treatment on the short- and long-term outcome of various types of febrile seizures. There is universal agreement that daily prophylaxis with antiepileptic agents should never be used routinely in simple febrile seizures, but only in highly selected cases, if at all. Intermittent diazepam (DZP) prophylaxis at times of fever may or may not reduce the recurrence rate, but it does not appear to improve the long-term outcome as compared with short-term seizure control. The treatment may be used to reduce the recurrence rate for a small arbitrarily defined group with multiple simple febrile seizures, complex febrile seizures, especially focal, prolonged or both, febrile status, and when parental anxiety is severe. However, there is no evidence that treatment of simple febrile seizures can prevent the rare cases of later epilepsy, and many children with complex febrile seizures have a benign long-term outcome, even without treatment. Many prefer a "wait and see" policy. An attractive alternative is to treat new febrile seizures with rectal DZP in solution at seizure onset, given by the parents at home to prevent febrile status. Newer, less well documented short-term strategies include nasal, oral, or rectal administration of other benzodiazepines. Short-term seizure control of febrile status and careful parental counseling are the two most important targets of treatment.

Epidemiologic, bacteriologic, and long-term follow-up data of children with acute hematogenous osteomyelitis and septic arthritis: a ten-year review.

A total of 69 children with acute hematogenous osteomyelitis and 48 with septic arthritis admitted in the period 1978 through 1987 were included in a retrospective review. Epidemiologic and bacteriologic data were analyzed and compared with those of an earlier study (1965 through 1975), confined to the same geographic area. Long-term outcome was evaluated by a questionnaire and clinical and radiographic follow-up. A significant increase in the admission rate for both disorders was observed. The long-term outcome was favorable: major sequelae were found in three patients (3%), minor sequelae in two patients (2%). The benign long-term outcome may well be related to rapid hospital admission and appropriate long-lasting antibiotic treatment.

Fish model for assessing the in vivo estrogenic potency of the mycotoxin zearalenone and its metabolites.

The in vivo estrogenic potency of zearalenone (ZEA), a mycotoxin produced by different strains of Fusarium fungi, and its metabolites (alpha- and beta-zearalenol), have been studied in fish. Estrogenicity was evaluated using an in vitro competitive receptor binding assay and in vivo induction of vitellogenesis and zonagenesis, two estrogen receptor (ER)-mediated responses that are integral aspects of fish oogenesis. The ER binding affinities of alpha-zearalenol and ZEA in rainbow trout (Oncorhynchus mykiss) were approximately 1/150 and 1/300 to that of estradiol, respectively. Juvenile salmon (Salmo salar) were exposed to a single intraperitoneal injection of ZEA, alpha-zearalenol and beta-zearalenol (each at 1 and 10 mg/kg) and compared to fish injected with estradiol-17 beta (E2; 5 mg/kg) and controls. Using indirect enzyme-linked immunosorbent assay (ELISA) with homologous antibodies, a dose-dependent induction of vitellogenin (Vtg) and eggshell zona radiata proteins (Zr-proteins) were observed 7 days after exposure to ZEA and alpha-zearalenol. beta-Zearalenol did not elevate plasma Vtg levels, but a non-significant elevation of plasma Zr-proteins levels was observed at the highest dose (10 mg/kg). Generally, alpha-zearalenol and ZEA possess estrogenic potencies that are approximately 50% compared to that of E2, and their order of estrogenic potency (in both in vitro receptor competitive binding and in vivo induction of Vtg and Zr-proteins levels) is: alpha-zearalenol > ZEA > beta-zearalenol. Our results show that blood plasma analysis of Vtg and Zr-proteins levels provides a suitable in vivo fish model for assessing the estrogenic potencies of ZEA and its metabolites.

[Clinical value of SPECT scanning in children with neurological disorders]. / Den kliniske vaerdi af SPECT-scanning hos børn med neurologiske sygdomme.

We retrospectively evaluated the clinical value of Tc-99-HMPAO brain single photon emission tomography (SPECT) in 21 children with neurological disorders of varied aetiology. All 21 patients were examined with electroencephalograms (EEGs), 17 with computed tomography (CT) and ten with magnetic resonance imaging (MR). New relevant information was obtained from SPECT in all 21 cases and in four of these cases the investigation directly led to a change in diagnosis and better assessment of the prognosis. It is concluded that SPECT is an important investigational method in children with neurological symptoms of partly or completely unknown aetiology.

[Shaken baby syndrome]. / Shaken baby syndrome--ruskede børn.

Shaken baby syndrome is a serious form of physical child abuse, which is frequently overlooked. It should be suspected in all children younger than one year of age, who present with drowsiness, coma, seizures or apnoea. A combination of subdural haematomas and retinal haemorrhages with minimal or no trauma and no coagulopathy is almost pathognomonic of the syndrome. The findings are caused by shaking with or without impact. Physical signs of violence are often absent and the syndrome may easily be mistaken for serious infection or seizure disorder. Many cases are fatal or lead to severe disability including blindness, cerebral palsy, mental retardation or epilepsy in about 60% of the children. There are many unresolved problems regarding diagnosis, pathophysiology, treatment, prognosis, prophylaxis and legal actions. We discuss these problems and in addition present eleven children with shaken baby syndrome.

[Incidence of child neglect and child abuse in the region of Copenhagen]. / Forekomst af omsorgssvigt mod børn oq børnemishandling i Københavns Amt.

The aim of the study was to evaluate the incidence of physical violence, neglect and sexual abuse against children as reported to the local authorities, in the county of Copenhagen during the year 1993. A questionnaire was mailed to the local authorities in the 18 districts in the county and to 18 schools and 18 general practitioners (GP's). They were asked whether, and how many new, verified and suspected cases of physical, emotional and sexual abuse had come to their attention in 1993. A total of 300 cases of child abuse were identified in the area with a total population of 675.000 i.e. a total incidence of 2.7 cases per 1000 children aged 0-17 years (2.7%), with 0.7% for physical violence, 0.5% for sexual abuse and 1.5% for emotional neglect. Some 180 cases were considered verified and 120 cases were suspected. A considerable variation between the different districts was noted, i.e. the local incidence varied from 0-5.4%. A statistically significant inverse correlation between the average local tax-income and the incidence of child abuse and neglect was found. There were several examples of schools having knowledge of more cases than the local authorities. Very few cases came to be attention of the GP.