Comparison of the timing of development of immunity in Romney lambs from resistant and resilient selection lines.

Variation in the timing of development of immunity to gastro-intestinal nematode parasites was assessed in resistant and resilient Romney selection lines exposed to mixed natural infection. From weaning, at mean 92 days-of-age, animals (n = 53) were sampled for faecal egg count (FEC) expressed as eggs per gram of faeces (epg), saliva for immunoglobulin (IgG and IgA) determination and fasted live weight (LW) every 10 days until 351 days-of-age. Overall, mean back-transformed FEC were consistently low for resistant animals (<200 epg) whereas resilient counterparts' FEC increased with time to reach a peak of 1400 epg at day 230 for females and 1800 epg for males at day 280 before declining to less than 500 epg by day 300, respectively (P < 0.001). Resistant lambs reached a threshold for Trichostrongylus colubriformis L3-specific IgG which was indicative of the presence of immunity earlier at 220.6 ± 8.8 days-of-age compared with resilient-line animals which reach this threshold 40 days later at 263.4 ± 6.9 days-of-age (P < 0.001). In addition, resistant females reached sexual maturity earlier compared with their resilient counterparts viz. 263.5 ± 3.7 c.f. 274.4 ± 3.4 days-of-age, respectively, (P = 0.048). Mean fasted live weight (LW) showed a selection line by time interaction (P < 0.001) which reflected greater LW in the early phase of the study in resilient males but increasing for all groups until day 280 before declining and being similar for all groups from day 330. In summary, differences appear to exist in the timing of immune development between these Romney lines, with resistant animals developing immunity earlier and these resistant-line animals also appear to be more physiologically mature at the same chronological age than resilient animals. These observations have implications on the timing of identification and selection of resistant animals.

First steps in designing a videophone for people with dementia: identification of users' potentials and the requirements of communication technology.

PURPOSE: To identify, based on the literature, people with dementia's potentials to manage an easy-to-use videophone, and to develop a videophone requirement specification for people with dementia. METHOD: The study is based on the Inclusive Design method, utilising the first two of four phases. Content analyses of literature reviews were used to identify users' potentials for managing a videophone and to gather recommendations regarding communication technology design for the target group. Existing videophones in Sweden were examined regarding potential fit to users with dementia. FINDINGS: This led to detailed identification of cognitive, physical and psychosocial challenges that people with dementia will probably have when using an ordinary telephone or videophone. A requirement specification for videophone design to fit users with dementia was formulated, with the seven principles of Universal Design as a framework. CONCLUSIONS: The requirement specification presented here is aimed at designing a videophone but might also facilitate design of other products for people with dementia, particularly in the field of communication technology. Based on this, further work will focus on developing a design concept and a prototype to be empirically tested by people with dementia and their significant others, i.e. the final two design process phases.

Impact of the apolipoprotein B/apolipoprotein A-I ratio on renal outcome in immunoglobulin A nephropathy.

OBJECTIVE: Serum levels of the apolipoprotein B/apolipoprotein A-I ratio (ApoB/ApoA-I) have been shown to identify patients at risk of cardiovascular disease. The aim of this study was to evaluate whether raised ApoB/ApoA-I values are also predictive of renal outcome in patients with chronic kidney disease (CKD), as similar mechanisms seem to be involved in the development of atherosclerosis and glomerulosclerosis. Only patients with immunoglobulin A nephropathy (IgAN) were included, since they represent a homogeneous group of patients with CKD. MATERIAL AND METHODS: ApoB and ApoA-I, serum albumin, urine albumin and blood pressure were measured, and a highly sensitive C-reactive protein test was carried out, in 70 patients with IgAN and in 70 age- and gender-matched healthy control subjects. Patients were followed over a period of up to 11 years (median 3.8 years). End-stage renal disease (ESRD) was defined as reaching CKD stage 5 [estimated glomerular filtration rate (eGFR) <15 ml/min/1.73 m²]. RESULTS: Baseline ApoB/ApoA-I values greater than 0.9 for men and greater than 0.8 for women were associated with a risk of developing CKD stage 5 (risk ratio 5.7, p = 0.037), independently of baseline GFR and serum albumin. CONCLUSION: Patients with IgAN and an increased ApoB/ApoA-I ratio have a significantly higher risk of developing ESRD compared with patients with a low ratio. Controlled studies are warranted to demonstrate whether interventions focusing on the ApoB/ApoA-I ratio may have beneficial clinical effects.

Atorvastatin-induced modulation of monocyte respiratory burst in vivo in patients with IgA nephropathy: a chronic inflammatory kidney disease.

BACKGROUND: IgA nephropathy (IgAN), the most common chronic inflammatory kidney disease, implies a considerable risk of renal failure and premature cardiovascular disease. Metabolic activation of monocytes has been suggested to be an important link between chronic inflammation, oxidative stress and the development of atherosclerosis. Oxidative stress is also involved in the progression of kidney disease. In this study we investigated the degree of monocyte activation, measured by monocyte respiratory burst in patients with IgAN, since these patients represent a fairly homogenous group of patients with chronic kidney disease, and compared the results to those in healthy subjects. As anti- inflammatory effects have been ascribed to HMG-reductase inhibitors, we also examined whether treatment with atorvastatin influenced monocyte respiratory burst. METHODS: Monocyte respiratory burst, unstimulated and stimulated by fMLP and PMA, was measured by flow cytometry in 16 patients with biopsy proven IgAN before and after 1 month of treatment with 20 mg atorvastatin/ day. Baseline values were compared to measurements in healthy subjects. Blood and urine samples, before and after statin treatment, were also analyzed for ox-LDL, inflammatory markers (CRP, MCP-1, ICAM-1, TNFR II and NGAL/MMP-9) and renal functional parameters. RESULTS: At baseline, respiratory burst of PMA-stimulated monocytes was higher in patients with IgAN as compared to that in healthy subjects (p = 0.002). After atorvastatin treatment there was a significant reduction of unstimulated, fMLP- and PMA-stimulated monocyte respiratory burst compared to baseline values (p = 0.03, p = 0.003 and p = 0.002, respectively). For ox-LDL and inflammatory serum markers we observed no significant changes. CONCLUSION: Our study demonstrates a higher monocyte respiratory burst in patients with IgAN compared to in cells from healthy controls as well as a significant reduction of this parameter after short time and low dose atorvastatin treatment.

Expression of iNOS mRNA associated with suppression of colonic contraction in rat colitis.

AIM: Nitric oxide (NO) synthesis and inducible NO synthase (NOS) expression are increased in colon of patients with inflammatory bowel disease (IBD) and associated with decreased contractility. The aim was to investigate which subtype of NOS that is activated in experimental colitis. METHODS: Experimental colitis was induced in Sprague-Dawley rats by Escherichia coli endotoxin. Expression of different subtypes of NOS was compared in normal and inflamed colon using reverse transcriptase-polymerase chain reaction. In organ baths, isometric contractile responses to acetylcholine (ACh) were studied in the colon, before and after incubation with the NOS inhibitor; N(omega)-nitro-L-arginine methyl ester (L-NAME) and NO donor glyceryl trinitrate. RESULTS: Inflammation decreased colonic contraction to ACh from a pD(2) value of 7.09 +/- 0.16 to 5.30 +/- 0.17 (P < 0.001), and reduced maximal response to ACh. Pre-treatment with L-NAME reversed contractility and shifted the pD(2) for ACh from 5.30 +/- 0.17 to 6.60 +/- 0.19 (P < 0.001) along with a normalized contraction efficacy. RT-PCR product of iNOS was obtained only in rats treated with endotoxin. CONCLUSION: Expression of iNOS is increased in inflamed colonic tissue. The induced overproduction of NO is likely to be responsible for the decreased motility in colitis where NO is suggested to exert a suppressive tone on colonic contractility, which is reversed by blockade of the enzyme.

Three-month neoadjuvant hormonal therapy before radical prostatectomy: a 7-year follow-up of a randomized controlled trial.

OBJECTIVE: To describe the outcome, assessed as the level of prostate specific antigen (PSA), of a mature (more than half the events recorded) prospective randomized study with a median follow-up of 82 months of neoadjuvant hormonal therapy before radical prostatectomy, as this has been suggested to decrease the rate of positive surgical margins (i.e. provide greater potential to completely excise the tumour). PATIENTS AND METHODS: From December 1991 to March 1994, 126 patients with clinically localized prostate cancer were randomized between direct radical prostatectomy or a 3-month course of a gonadotrophin-releasing hormone analogue before surgery. The patients were followed by PSA determinations and a value of > 0.5 ng/mL used to define progression. RESULTS: The incidence of positive surgical margins decreased from 45.5% to 23.6% (P = 0.016) with hormone treatment. Despite this there was no difference in PSA progression-free survival at the last follow-up; it was 51.5% for those undergoing radical prostatectomy only and 49.8% for those who received hormonal pretreatment (P = 0.588). CONCLUSIONS: Three months of neoadjuvant hormonal therapy before radical prostatectomy offers no benefit to the patient and cannot be recommended for routine clinical use.

Regressive changes and neuroendocrine differentiation in prostate cancer after neoadjuvant hormonal treatment.

BACKGROUND: We studied the extent of neuroendocrine (NE) tumor cell differentiation and its relation to regressive changes in prostate cancer after 3-month hormonal treatment. METHODS: Radical prostatectomy specimens from 103 patients, randomized to 3-month neoadjuvant LH-RH-analogue treatment (neoadjuvant group) or to surgery alone (control group), were available for analysis. The effects of hormonal treatment in terms of positive surgical margins, the degree of histopathological changes, and tumor cell proliferation were evaluated in relation to NE-differentiation assessed with antibodies against chromogranin A (CGA). RESULTS: Both the number of CGA-positive cells/cm(2) (P < 0.003) and the proportion of NE-positive tumors (P = 0.07) were greater in the neoadjuvant group than in the control group. No correlation existed between NE-differentiation and the effects of the neoadjuvant hormonal treatment; nor did NE-differentiation correlate to the decrease in serum PSA. CONCLUSIONS: Neuroendocrine differentiation in prostate cancer increases after 3 months of neoadjuvant hormonal treatment but does not correlate to the effects of hormonal treatment.

Neuroendocrine differentiation is not prognostic of failure after radical prostatectomy but correlates with tumor volume.

OBJECTIVES: To study neuroendocrine (NE) tumor cell differentiation in prostate cancer in relation to failure after radical prostatectomy. METHODS: Radical prostatectomy specimens from 103 of 111 patients randomized to 3-month neoadjuvant luteinizing hormone-releasing hormone-analogue treatment (neoadjuvant group) or to surgery alone (control group) were available for analysis. Immunohistochemistry using antibodies to chromogranin A (CGA) enabled detection of tumor cells with NE differentiation. NE differentiation was scored as NE-negative (0 to 1+) or NE-positive (2 to 3+). The number of CGA-positive cells/cm(2) tumor area on the slides was assessed in a separate analysis. The patients were followed up for 39 months after surgery, and a prostate-specific antigen value of 0.5 ng/mL or greater in two consecutive blood samples was considered biochemical failure. RESULTS: Kaplan-Meier analysis stratified for neoadjuvant hormonal treatment showed the failure rate to be significantly greater among those with NE-positive tumors than among those with NE-negative tumors. However, the number of CGA-positive cells/cm(2) was not a variable of prognostic significance. Instead, both NE differentiation and the CGA-positive cell count correlated with the tumor area on the slides (P = 0.0001). Multivariate analysis revealed the tumor area on the slide (P <0.0001) and positive surgical margins (P = 0.03) to be the only significant predictors of biochemical failure. CONCLUSIONS: The extension of NE differentiation in prostate cancer correlates with tumor volume and is not an independent prognostic factor of failure after radical prostatectomy.

MRI in rolandic epilepsy.

Hippocampal and/or white matter abnormalities have been found on the MRIs in 10/18 children with typical rolandic epilepsy. The etiology of the first-mentioned is not evident, whereas the latter may be a result of a maturational delay involving a defective myelination. Both abnormalities may cause cognitive dysfunction. In order to get a better understanding of rolandic epilepsy both MRI and neuropsychological studies are wanted in groups of children with typical rolandic seizures with and without rolandic sharp waves, as well as in groups of children with typical rolandic sharp waves and atypical seizures.

Hippocampal asymmetries and white matter abnormalities on MRI in benign childhood epilepsy with centrotemporal spikes.

PURPOSE: To look for brain abnormalities by using magnetic resonance imaging (MRI) in patients with benign childhood epilepsy with centrotemporal spikes (BCECTS), which is the most common epilepsy syndrome in children. METHODS: Eighteen children, aged 6-12 years, with typical BCECTS were examined with MRI, six of them twice. RESULTS: Some hippocampal abnormality was found in six (33%) of the children, all with the syndrome's typical electroencephalogram (EEG) pattern ipsilaterally. Hippocampal size asymmetry was found in five (28%) children (right side < left in two and left < right in three), and high signal intensities on T2-weighted images were found in three (17%). Two children also had other abnormalities; one had a heterotopic nodule near the contralateral frontal horn, and one had an Arnold-Chiari malformation. The hippocampal asymmetry remained unchanged in three of the children who were reexamined after 2 years. High signal intensities on T2-weighted images were seen beneath the cortex-white matter junction in the frontal and temporal lobes of five (28%) children, one of whom also had a hippocampal asymmetry. MRIs were normal in eight (44%) children. CONCLUSION: For the first time, hippocampal asymmetries and white-matter abnormalities have been detectable on the MRIs of children with typical BCECTS. The etiology of the former is unclear, whereas the latter may be a result of a maturational delay involving a defective myelination. Long-term follow-up studies are needed to evaluate the relation between these findings and the clinical course of BCECTS.

Tumor cell proliferation in prostate cancer after 3 months of neoadjuvant LHRH analogue treatment is a prognostic marker of recurrence after radical prostatectomy.

OBJECTIVES: To evaluate tumor cell proliferation in relation to histopathologic regressive changes and failure after radical prostatectomy after a 3-month course of neoadjuvant luteinizing hormone-releasing hormone (LHRH) analogue treatment. METHODS: We evaluated slides from 103 radical prostatectomy specimens of the 111 patients participating in a randomized trial of a 3-month course of neoadjuvant LHRH analogue treatment before radical retropubic prostatectomy (n = 50) versus surgery alone (n = 53). The histopathologic regressive changes in the specimens were scored by two pathologists. Sections were stained with the anti-Ki-67 monoclonal antibody MIB-1. The proliferation index (PI) was defined as the proportion of Ki-67-positive cells in a random cell count. The patients were followed up until treatment failure or for a mean of 39 months among those without failure. RESULTS: In the neoadjuvant group, increasing histopathologic regressive changes correlated with a decrease in capsular penetration, positive surgical margins, and tumor cell proliferation but did not correlate with Gleason score in biopsies. Treatment failure was not related to the histopathologic regressive changes. In the neoadjuvant treatment group, progression-free survival was longer in the subgroup of patients with tumors with a PI less than 1.2% compared with those with tumors with a PI greater than 1.2% (P = 0.02). Multivariate analysis of PI and histopathologic and clinical features showed the PI (P = 0.002) and the pretreatment serum prostate-specific antigen level (P = 0.003) to be significant prognostic markers of failure in the neoadjuvant group. CONCLUSIONS: Tumor cell proliferation after 3 months of neoadjuvant hormonal treatment is a prognostic marker of failure after radical prostatectomy without correlation to Gleason score or the histopathologic regressive changes resulting from hormonal treatment.

The chemotactic response of Vibrio anguillarum to fish intestinal mucus is mediated by a combination of multiple mucus components.

Chemotactic motility has previously been shown to be essential for the virulence of Vibrio anguillarum in waterborne infections of fish. To investigate the mechanisms by which chemotaxis may function during infection, mucus was isolated from the intestinal and skin epithelial surfaces of rainbow trout. Chemotaxis assays revealed that V. anguillarum swims towards both types of mucus, with a higher chemotactic response being observed for intestinal mucus. Work was performed to examine the basis, in terms of mucus composition, of this chemotactic response. Intestinal mucus was analyzed by using chromatographic and mass spectrometric techniques, and the compounds identified were tested in a chemotaxis assay to determine the attractants present. A number of mucus-associated components, in particular, amino acids and carbohydrates, acted as chemoattractants for V. anguillarum. Importantly, only upon combination of these attractants into a single mixture were levels of chemotactic activity similar to those of intestinal mucus generated. A comparative analysis of skin mucus revealed its free amino acid and carbohydrate content to be considerably lower than that of the more chemotactically active intestinal mucus. To study whether host specificity exists in relation to vibrio chemotaxis towards mucus, comparisons with a human Vibrio pathogen were made. A cheR mutant of a Vibrio cholerae El Tor strain was constructed, and it was found that V. cholerae and V. anguillarum exhibit a chemotactic response to mucus from several animal sources in addition to that from the human jejunum and fish epithelium, respectively.

Booster vaccination with recombinant hepatitis B vaccine four years after priming with one single dose.

We here studied the antibody response to a booster dose four years after the administration of one single dose of recombinant HB vaccine. Before receiving the booster dose, levels of protective antibodies (anti-HBs) were generally low and 24/41 (59%) individuals lacked detectable antibodies (< 1 IU/L). Within 14 d of booster vaccination, 36/38 (95%) vaccinees showed levels of antibodies > 100 IU/L. Notably, these levels were at least as high as those of a reference group 12 months after initiation of vaccination according to the standard three-dose vaccination at intervals of 0, 1 and 6 months. In conclusion, one single dose of HB vaccine seemed to confer on young healthy individuals a well preserved B cell memory, disclosed as a rapid and strong antibody response to a second dose four years later.

[Increasing infant mortality and tuberculosis in China. A dark picture of public health and health care in China]. / Okande antal fall av spädbarnsdöd och tuberkulos i Kina. Mörk bild av folkhälsa och sjukvård i Kina.

PIP: Lennart Bogg, a prominent researcher at the Karolinska Institute, has been monitoring the development of public health in China since 1984. According to Bogg, the increase in the infant mortality rate in China (from 34.7/1000 children in 1981 to 37.0/1000 children in 1992) and the increase in the number of cases of tuberculosis and schistosomiasis are signs of deteriorating public health. Infant mortality has reached 72/1000 in the interior, but it is only 15/1000 in the large cities: this is indicative of a gap in health care delivery in the country. The number of cases of tuberculosis has increased significantly in recent years, and the disease causes 360,000 deaths per year. In the meantime, though, average life expectancy rose between 1949 and 1982, from 39 to 69 years. In the mid 1960s, collective health insurance and the so-called barefoot doctors system were introduced in the rural areas, with 90% of the villages being served by the system. Simple preventive health care and basic care was financed by this system. Subsequent to the reforms introduced in the late 1970s, the collectives were replaced by an individual contract system for each household, and the health insurance system was dismantled without there being anything else to replace it. Nowadays it is estimated that 10-15% of people are insured; these are mainly people who work in cities. The fee-for- service scheme boosted health care costs eight times between 1983 and 1990. Quality of maternal and child health care has declined in the rural areas, and most deliveries take place in the home with the assistance of untrained personnel. In the countryside even the one-child policy seems to have collapsed. In 1994 a project that aimed at resurrecting cooperative health insurance was initiated^ieng

Neuropsychological findings in children with benign childhood epilepsy with centrotemporal spikes.

Benign childhood epilepsy with centrotemporal spikes (BCECTS) is a well-known idiopathic age- and localization-related epileptic syndrome with characteristic clinical and EEG manifestations. Due to the reported benign evolution of this epilepsy syndrome, neuropsychological assessment has been considered unnecessary. However, the benign nature of BCECTS has recently been challenged: verbal dysfunction as well as impaired visuomotor coordination, specific learning disabilities, and attention deficit have been noticed. These findings prompted this research study in which all children with BCECTS attending our epilepsy clinic underwent neuropsychological assessment. Seventeen children (10 boys and seven girls) aged 7 to 14 years were investigated with a neuropsychological test battery focusing on immediate and delayed recall of auditory-verbal and visual material, verbal fluency, problem-solving ability, and visuospatial constructional ability. Raven's coloured matrices and questionnaires regarding school functioning and behaviour were also administered. The children were matched with control subjects for age, sex, and school. Children with BCECTS had significantly lower scores than their control subject partners on the neuropsychological items. Intellectual abilities did not differ and neither did school functioning or behaviour according to teachers. Parents, however, recognized greater difficulties with concentration, temperament, and impulsiveness in children with BCECTS.

Falloposcopy in conjunction with laparoscopy: possibilities and limitations.

Falloposcopy is a transvaginal microendoscopic technique to explore the human Fallopian tube from the uterotubal ostium to the fimbrial end. Falloposcopy provides a unique possibility to visualize endotubal disease and may be used therapeutically for removal of debris and for cutting down filmy intraluminal adhesions. To assess the clinical performance of falloposcopy as part of an infertility investigation, a total of 43 women scheduled for laparoscopy as part of an investigation of infertility had a falloposcopy performed in conjunction with the laparoscopy. All women were investigated at Danderyd Hospital, Stockholm and Akademiska Hospital, Uppsala, during 1995 and 1996. Images from the endosalpinx were obtained in 26 of 43 women (60.5%). In 10 women (23.3%), it was possible to obtain images from both tubes. No images were of sufficient quality to describe the entire tubal mucosa in detail. Falloposcopy represents a unique tool for visualization of endotubal disease and may provide a valuable instrument for in-vivo exploration of tubal physiology. However, certain technical problems limit the usefulness of this method in routine clinical practice. These technical problems have to be solved before falloposcopy can achieve a central position in investigation and treatment of tubal disease.

Population dynamics of resource limited plants and their pollinators.

In this paper we build upon and generalize an earlier model of the interactions between a plant and its pollinator (Ingvarsson and Lundberg, 1995). In this model we assume that the performance of the pollinator population is directly linked to the size of the plant population. To avoid the problem of both populations growing exponentially we have, without loss of generality, assumed the plant population to be resource limited. Analysis of the system shows that there exists either two or no internal equilibrium points. The case with no equilibrium points corresponds to the trivial case where the system cannot persist, resulting in the extinction of both the plant and pollinator population. When the two internal equilibrium points do exist, one of them will always be unstable. This unstable equilibrium can be viewed as an equivalent of the threshold criteria derived in Ingvarsson and Lundberg (1995) in the sense that whenever the system is initiated above the unstable equilibrium point, persistence of the system is assured, while both species will go extinct whenever the system is initiated below the unstable equilibrium point. The analytical results were verified by numerical simulations of the system. We conclude that the existence of a threshold criteria, below which the system cannot persist is a general feature of plant-pollinator systems. We discuss how the existence of the threshold criteria will affect the persistence of plant-pollinator systems in light of, for instance, habitat fragmentation or stochastic reductions in the densities of either the plant or pollinator population. We further highlight some recent empirical studies that indicate the existence of a threshold in natural populations below which extinction is inevitable.

Hormonal treatment before radical prostatectomy: a 3-year followup.

PURPOSE: Hormonal treatment administered before radical prostatectomy has been shown to decrease the rate of positive surgical margins. We determine whether preoperative hormonal treatment has any impact on the subsequent failure rate. MATERIALS AND METHODS: We prospectively evaluated 122 patients with stages T1bNxM0 to T3aNxM0, grades 1 to 3 prostate cancer, including 64 randomly assigned to immediate radical retropubic prostatectomy and 58 randomly assigned to radical retropubic prostatectomy preceded by 3 months of pretreatment with a gonadotropin-releasing hormone agonist. We performed intention to treat analysis on the data with failure defined as lymph node involvement, serum prostate specific antigen greater than 0.5 ng./ml., or the need for postoperative hormonal or radiation adjuvant treatment. RESULTS: The positive margin rate was 23.6 versus 45.5% in the pretreatment plus prostatectomy versus prostatectomy only groups (p = 0.016). There were 20 failures (34.5%) in the pretreatment plus prostatectomy subgroup and 26 (40.6%) in the prostatectomy only group (p = 0.48). A negative surgical margin was associated with a significantly lower risk of progression than a positive surgical margin (20.8 versus 50.0%, p = 0.0016), and progression was delayed by approximately 1 year after hormonal pretreatment. However, at a median followup of 38 months there was no difference in progression-free survival (p = 0.57). CONCLUSIONS: Although hormonal pretreatment significantly decreased the positive margin rate, it did not result in any difference in progression-free survival when followup exceeded 3 years. Thus, our current results do not support the routine administration of hormonal treatment before radical prostatectomy.