Ki67 and p53 immunohistochemistry reduces interobserver variation in assessment of Barrett's oesophagus.

AIMS: To devise clinically applicable methods for assessing p53 and Ki67 immunohistochemical (IHC) reactivity in Barrett's oesophagus (BE) and to compare the interobserver agreement between these methods and routine haematoxylin and eosin (H&E) evaluation. METHODS AND RESULTS: One hundred and fifteen biopsies diagnosed as BE, selected from the files of the University Hospital MAS, Malmo, were re-evaluated for dysplasia by three pathologists. For IHC analysis areas with the most prominent positivity were evaluated. The mean of p53+ epithelial nuclei/high-power field (HPF) was obtained by counting between 1 and 5 HPFs/biopsy. A proliferation quotient (PQ) was obtained by dividing the number of Ki67+ epithelial nuclei in the upper half by the lower half of the mucosa, using two HPFs. Mean kappa values were 0.24, 0.71 and 0.52 for H&E, p53 and Ki67 evaluations, respectively. There was a correlation between increasing severity of dysplasia, IHC measurable overexpression of p53 and shift of the mucosal proliferation zone towards the surface, measured as PQ. CONCLUSIONS: The described methods for p53 and Ki67 evaluation are more reproducible than routine H&E evaluation of BE. Furthermore, the IHC methods correlate with the severity of dysplasia and are useful supplementary prognostic markers.

Management of children with dilating vesico-ureteric reflux in Sweden.

AIM: To evaluate the management and outcome of children with dilating vesico-ureteric reflux diagnosed before 2 y of age. METHODS: This retrospective, multicentre study was part of a programme for quality assurance in Sweden. A total of 2309 unselected children, aged 0-2 y, were investigated after the first urinary tract infection. Voiding cystourethrography was performed in a total of 1953 children, of whom 584 had reflux. Of these children, 303 (119 boys and 184 girls) had reflux with dilatation (grade 3-5). RESULTS: Follow-up after 4-6 y was reported in 272 of the 303 children. Spontaneous regression of dilating reflux occurred in more than half of the patients and was significantly more frequent in boys than in girls (p = 0.047). In children with grade 3 reflux and grade 4-5 reflux, there were pyelonephritic recurrences in 18% and 45% of the boys and 28% and 70% of the girls, respectively (p < 0.001). One hundred and eighty-one children (65%) were managed conservatively, 58 (21%) were treated with subureteric injection and 33 (12%) with ureteric reimplantation. There were considerable differences in treatment strategies between centres. CONCLUSION: This study of an unselected cohort of children with urinary tract infection and dilating reflux showed spontaneous resolution of dilating reflux in more than half of the subjects and more often in boys than in girls. Pyelonephritic recurrences were more common in girls than in boys, and more frequent in grade 4-5 reflux than in grade 3. The results indicate important differences between the sexes and that boys and girls should be assessed separately when treatment strategies are studied.

Chronology of particle emission from the E/A=61 MeV 36Ar+27Al reaction.

The emission time chronology of neutrons, protons, and deuterons from the E/A=61 MeV 36Ar+27Al reaction is deduced from two-particle correlation functions.

Improved cooperation in vocational rehabilitation with systematic rehabilitation group meetings.

PURPOSE: The present aim was to investigate the communicative pattern in two rehabilitation groups. The rehabilitation group consisted of the client, a supervisor, an employer representative, an occupational health physician, a rehabilitation counsellor from the national social insurance office and a support person. METHOD: Participatory observation of 22 rehabilitation meetings. The communication was tape-recorded and transcribed word for word. The transcripts were coded and analysed both qualitatively and quantitatively. RESULTS AND CONCLUSION: The client made the most utterances in the groups, but most often in the form of answers to questions from the other actors. Following the client, the physician made the next most frequent utterances, most often as questions. The subjects most discussed concerned the client's situation regarding work, health and material support. None of the "professionals" dominated the meetings, although one picture that emerged was that the physician and employer representative played more prominent roles as takers of initiative and as coordinators while the client was more passive than the other actors. The discussions were calm and much latitude was allowed for the participants to put forward their own requirements, thoughts and feelings. The rehabilitation group may be viewed as a meeting place for "experts" and clients. The further management of the rehabilitation was by the actor the client most immediately needed. In this, rehabilitation in the rehabilitation group differs from the "case management" common in the rehabilitation field.

Successful treatment of restless legs syndrome with an implanted pump for intrathecal drug delivery.

Two patients with incapacitating symptoms from restless legs syndrome, not adequately responding to conventional treatment with dopaminergic drugs, were implanted with a pump device (Isomed) for intrathecal delivery of morphine and bupivacaine. The treatment resulted in total resolution of all symptoms with few side effects.

Possibility to deduce the emission time sequence of neutrons and protons from the neutron-proton correlation function.

Experimental information has been derived from the neutron-proton correlation function in order to deduce the time sequence of neutrons and protons emitted at 45 degrees in the E/A = 45 MeV 58Ni + 27Al reaction.

Studies of the radon concentration in drinking water from the horst Söderåsen in southern Sweden.

The radon activity concentration in ground water from drilled and dug wells on the horst Söderåsen in Southern Sweden has been determined with two different methods, gamma activity measurements with a germanium HPGe detector and alpha activity measurements with plastic track detectors. The results are consistent. High activity concentration is connected to granite bedrock. Dug wells have low concentrations and no trivial correlation between concentration and depth of the well is found. Large local variations exist. Activity concentrations > 700 Bq/l appear to be associated with leakage from layers of volcanic origin. The concentration from drilled wells is found to be quite constant over a 3 year period but short time variations appear to be significant. Evaporation from the open surface of a normal cooking vessel is slow with an activity gradient delta A/A of about 0.1-0.2 per hour at room temperature whereas even modest heating of water in e.g. a coffee machine is very efficient and reduces the radon activity concentration by > 90% in one process.

Low level of bacterial contamination of mist tents used in home treatment of cystic fibrosis patients.

Mist tents are recommended by the Stockholm cystic fibrosis (CF) centre for small children with CF. Daily disinfection of some parts of the tent with 2% acetic acid is recommended, and for other parts boiling water followed by air-drying without rinsing. The plastic tent is discarded each day. We have studied whether these prescribed routines are followed by the patients and whether they are sufficient to prevent bacterial contamination. The mist tent equipment of 20 CF patients (mean age 7 years, range 1-15 years), two of whom were chronically colonized with Pseudomonas aeruginosa, were investigated. All patients were visited at home in the morning after 6-12 hours aerosol therapy. Liquid from the nebulizing chambers and swabs from the aerosol tube were examined by culture on four different media. Seventeen of 20 patients claimed that they cleaned and disinfected the tubes every day, two patients every other day and one once a week. Seventeen of 19 claimed they cleaned and disinfected the chambers daily, one once a week and, one twice a week. No or insignificant growth was found in 16/20 aerosol tubes: moulds in three, Pseudomonas species in one. Twelve of 19 chambers showed no or insignificant growth: moulds or yeasts were present in three and Pseudomonas sp. in four. In four of the seven patients moulds or yeasts and/or Pseudomonas sp. grew both from chambers and from aerosol tubes; in the remaining three only from chambers. None of these seven patients had followed our prescribed cleaning and disinfection recommendations, the other 13 claimed they had. Of the patients whose equipment yielded Pseudomonas sp, none was colonized with these strains, although one had P. aeruginosa. We conclude that our disinfection recommendations are adequate when followed. However, our disinfection recommendations concerning the nebulizing chamber had not been followed satisfactorily. The different forms of non-compliance would not have been detected without a home visit, emphasizing the importance of such visits. The importance of drying the equipment and of using the correct concentration of acetic acid is stressed.

Imaging of renal scarring.

Children with urinary tract infection should be investigated and followed up, as those with pyelonephritis may develop renal scarring. In this review, after discussing the advantages and disadvantages of various imaging modalities for diagnosis of renal scarring, it is concluded that DMSA scintigraphy and urography can both be used to detect significant renal scarring. With DMSA scintigraphy, small renal lesions (functional uptake defects) not seen at urography will also be detected. The long-term clinical significance of these lesions is, as yet, unknown. A normal DMSA scintigraphy after infection indicates low risk for clinically significant damage. In order to allow acute, reversible lesions to first disappear, a follow-up DMSA examination should not be performed until at least 6 mo after the acute infection. Ultrasonography in isolation cannot be recommended for the diagnosis of renal scarring.

Vesico-ureteric reflux: occurrence and long-term risks.

The prevalence of vesico-ureteric reflux in the general population is unknown, but it is increased in risk groups, such as children with symptomatic urinary tract infection, schoolgirls with asymptomatic bacteriuria, first-degree relatives of patients with reflux and children with prenatal dilatation of their upper urinary tract. Children and adults with pyelonephritic renal scarring are at risk of serious long-term complications, e.g. hypertension and renal failure. Modern paediatric care, with early detection and treatment of urinary tract infections and reflux during childhood and adolescence, may improve long-term prognosis. In the adult patient with established pyelonephritic renal scarring, careful control of hypertension may retard the rate of progression, and angiotensin converting enzyme inhibitors may have renal protective properties.

Vesico-ureteric reflux and other risk factors for renal damage: identification of high- and low-risk children.

This article reviews the literature with respect to various risk factors for permanent renal damage in children with urinary tract infection. Vesico-ureteric reflux is an important risk factor, but renal damage can occur in the absence of reflux. Renal damage does not always occur in the presence of gross reflux. Renal scars always develop at the same site as a previous infection in the kidney. Recurrent pyelonephritis and delay in therapy increase the likelihood of renal damage, although it is not known how long a delay is dangerous to the human kidney. Recent studies using 99mtechnetium-dimercaptosuccinic acid (DMSA) scintigraphy have not confirmed the findings of previous studies showing that children below 1 y of age are more vulnerable to renal damage. It is more likely that all children run the risk of renal scarring in cases of acute pyelonephritis. The role of bladder pressure is still not entirely understood. Therefore more studies are needed in order to determine the relationship between high voiding pressures in some, otherwise healthy, children with urinary tract infection and renal scarring. The importance of bacterial virulence in the development of renal scarring is unclear. DMSA scintigraphy and voiding cystourethrography are the most reliable tools for identifying children at risk of renal scarring. As a single method DMSA scintigraphy appears to be better than voiding cystourethrography.

Minimum incidence and diagnostic rate of first urinary tract infection.

OBJECTIVE: To study awareness of urinary tract infections (UTIs) by determining the diagnostic rate of first UTI in children <2 years of age and to estimate the minimum incidence. METHODS: Twenty-six of a total of 43 pediatric centers participated in the study. Sixty-four percent of the total childhood population <2 years of age was covered. The number of all children included in the study was used to calculate the diagnostic rate. Only UTI confirmed by either suprapubic aspiration (any growth) or midstream or bag samples with >/=100 000 bacteria/mL, together with a positive nitrite reaction, was used to estimate the minimum incidence. RESULTS: The mean diagnostic rate was 1.5% for boys (range, 0.7%-3.0%) and 1.7% for girls (range, 0.7%-2.9%). The diagnostic rate was significantly higher in June than in December. The mean incidence was 1.0% for both boys and girls (range, 0.3%-3.0% and 0.4%-2.9%, respectively). The minimum cumulative incidence at 2 years of age was estimated to be 2.2% for boys and 2.1% for girls. CONCLUSION: This study suggests a high UTI awareness in Sweden as indicated by a higher diagnostic rate and, despite stricter diagnostic criteria, a higher incidence of UTI in children <2 years of age than previously reported. It is suggested that a high UTI awareness may reduce chronic renal failure because of pyelonephritic renal scarring.

Urinary tract infections in children below two years of age: a quality assurance project in Sweden. The Swedish Pediatric Nephrology Association.

The objective of this study was to evaluate the basis for diagnosis and assessment of children <2 y of age with urinary tract infections (UTI) and to describe their subsequent management as currently practised in Sweden. The study was a prospective, multicentre project as part of a programme for quality assurance. A total of 2309 children (1111M, 1198F) was studied during a 2-y period. Of the population at risk, 1.6% of both boys and girls were diagnosed with a UTI. This represents a minimum figure. Suprapubic bladder aspiration was mainly used during the first year of life, with the highest frequency in the youngest infants. Adhesive bags were used in half of the children, and the frequency increased with age. Imaging of the urinary tract was performed in 97% of the children. Vesicoureteric reflux was the most common finding, occurring in 36% of the girls and 24% of the boys. The presence of dilatation of the upper urinary tract correlated significantly to the presence and grade of reflux. Initial intravenous therapy was given to 31% of the children and long-term antibacterial prophylaxis to 20%. Major differences were found between centres in diagnostic rate, urine sampling technique and the use of parenteral therapy. In conclusion, this study showed a high diagnostic rate of urinary infections in children below 2 y of age. The urine sampling technique was optimal (suprapubic aspiration) in half of the infants, but less reliable in the children above 1 y of age. The frequency of imaging investigations of the urinary tract was high. The strategies for diagnosis and treatment varied considerably among centres.

Transient pyelonephritic changes on 99mTechnetium-dimercaptosuccinic acid scan for at least five months after infection.

A prospective study was performed on 185 children with symptomatic urinary tract infection (UTI), 130F and 55M, having a median age of 0.9 y (range 0.1-9.8) at the time of UTI. The aim of the study was to find out how the 99mTechnetium-dimercaptosuccinic acid (DMSA) scan should be used to investigate UTI, and to follow the development of renal changes during pyelonephritis into subsequent permanent renal damage. All children were investigated with a DMSA scan within 5 days after admission and after 3.9-53.3 (median 9.2) weeks, and 159 were studied again after approximately 2 y (range 1.5-3.9 y). They all underwent micturition cystourethrography at the time of the second study. At the time of infection, the DMSA scan was abnormal in 85% of the children, in 58% at the first follow-up and in 36% at the second follow-up. An abnormal DMSA scan performed within 20 weeks from infection became normal in 38% of cases on the third study, while only 1/10 abnormal DMSA scans performed more than 20 weeks after infection became normal after 1.5-3.9 y. Persistent renal changes were more common in children > 4 y of age than in children < or = 1 y of age. Two months after the presenting infection, it was unusual to see a normal DMSA scan in a child with a VUR gr. > or = 3. The study suggests that DMSA changes after an index UTI may be transient for a longer period of time than has been previously considered. Therefore, in order to detect persistent changes, a DMSA scan should be performed more than 5 months after UTI.

Low bacterial contamination of nebulizers in home treatment of cystic fibrosis patients.

Many reports have shown bacterial contamination of nebulizers used by patients with cystic fibrosis (CF) at home. At the Stockholm CF centre we recommend dismantling the equipment, washing, rinsing and drying it after each use, and disinfecting it once daily by boiling water or by 2% acetic acid followed by drying without rinsing. We studied whether patients comply with these recommendations and whether they are sufficient to prevent bacterial contamination. Nebulizers from 49 CF patients were investigated, 21 of whom are chronically colonized with Pseudomonas aeruginosa and one with Burkholderia cepacia. All patients were visited at home. Thirty-nine patients (79%) disinfected their equipment after the latest use in accordance with our recommendations. Thirty-eight pieces showed no, or only scanty, growth of micro-organisms belonging to the normal oropharyngeal flora. A moderate growth of alpha-streptococci was observed from a further five pieces. Four of these had not been cleaned after the latest inhalation occasion, and one was visibly dirty. Pseudomonads were observed from three pieces; two of these had been disinfected by boiling water and one by acetic acid, followed by rinsing in tap water. All three had been inadequately dried. Pseudomonads could not be cultured simultaneously from the sputum of these three patients. In conclusion, most patients comply with our cleaning and disinfection recommendations and these recommendations appear satisfactory in preventing bacterial contamination.

Effect of hydrochlorothiazide and indomethacin treatment on renal function in nephrogenic diabetes insipidus.

The purpose of this study was to investigate the effects of treatment with hydrochlorothiazide and hydrochlorothiazide and indomethacin combined on renal function in four boys, two with nephrogenic diabetes insipidus and two with partial nephrogenic diabetes insipidus using the clearances of inulin and para-aminohippuric acid under water diuresis and lithium clearance. Hydrochlorothiazide reduced urine flow and lithium clearance. These effects were further potentiated by addition of indomethacin. No consistent effects on renal plasma flow or glomerular filtration rate were found. It is concluded that treatment with hydrochlorothiazide alone and hydrochlorothiazide and indomethacin combined reduces urine flow in nephrogenic diabetes insipidus by increasing proximal tubular reabsorption of sodium.