[Do dare to perform myomectomy vaginally!].
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Biomedical subjects
Publications and source records attributed to S Lundberg.
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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.
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.
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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.
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.
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.
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.
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.
OBJECTIVE: To investigate whether radionuclide hysterosalpingography (radionuclide HSG), which has been suggested as a more functional approach to the diagnosis of tubal infertility than conventional patency tests, is predictive in the diagnosis of infertility. DESIGN: A retrospective analysis of data from an inquiry form containing questions about pregnancy outcome after radionuclide HSG. SETTING: University hospital-based, tertiary care infertility clinic. PATIENT(S): Two hundred sixteen women had an infertility work-up including radionuclide HSG performed between April 1986 and April 1993. Forty-one (18.9%) women were excluded from the study; 9 had moved to unknown addresses, 16 did not answer the inquiry, and 16 gave answers that were not interpretable. There were 175 (81.1%) women in the final study group. INTERVENTION(S): An inquiry form containing questions regarding pregnancy was sent to 207 women who undergone radionuclide HSG as a routine procedure in their infertility workup. MAIN OUTCOME MEASURE(S): Occurrence of pregnancy related to outcome of radionuclide HSG and its test properties calculated. RESULT(S): Bilateral or unilateral tubal transport was demonstrated by radionuclide HSG in 129 women, of whom 66 (51%) later became pregnant. Of the pregnant women, 36 (55%) had successful infertility treatment, whereas 30 (45%) reported spontaneous pregnancy. Forty-six women showed no transport at radionuclide HSG. Twenty-five (54%) of these women became pregnant, 14 (56%) with infertility treatment and 11 (44%) without infertility treatment. The predictive values of transport and no transport radionuclide HSG were 0.51 and 0.46, respectively. The sensitivity of radionuclide HSG was 0.25, and the sensitivity was 0.73. Likelihood ratios for pregnancy when radionuclide HSG showed transport and no transport were 1.03 and 0.93, respectively. CONCLUSION(S): Our data strongly indicate that a single radionuclide HSG investigation is not able to predict fertility potential.
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.
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.
We have used circular dichroism and 1H- and 15N-NMR spectroscopy to investigate calcium binding to the two EF-hands of human nonerythroid or alphaII-spectrin. Comparison of the 1H-NMR spectra from the peptide containing both EF-hands to the peptides containing the single EF-I and EF-II structures showed that both the structural and calcium-binding properties are significantly different. Further studies of the 121 amino acid peptide containing both EF-hands using circular dichroism and NMR showed that the binding of calcium ions induces conformational changes. To investigate the calcium-binding mechanism, the chemical shifts changes were recorded using multidimensional NMR spectroscopy during calcium titration. A total of 25 titration curves were obtained, each corresponding to the chemical shift changes of individual amino acid residues. The shapes of these titration curves were either hyperbolic or sigmoidal. Using factor analysis, two functions were extracted, one hyperbolic and one sigmoidal, which accounted for nearly all information present in the titration curves. By fitting the two functions to binding curves based on different binding models, we found that the binding mechanism is best described as sequential. Since the sigmoidal type was more pronounced in the titration curves corresponding to residues from the first EF-hand, we suggest that calcium binding to the first EF-hand is described by the sigmoidal function, and that the hyperbolic function describes calcium binding to the second EF-hand. Therefore, is seems likely that the second EF-hand must contain bound calcium before the first EF-hand can bind.
The female genital tract is capable of active transport that can be demonstrated by serial scintigraphic imaging over time (radionuclide hysterosalpingography; RN-HSG). RN-HSG has been suggested to offer a more functional approach to tubal infertility diagnosis than conventional patency tests. However, before RN-HSG can be recommended as a routine method, its reliability in showing active transport in fertile women must be demonstrated. Therefore we compared RN-HSG in two groups: 38 fertile women before tubal sterilization and 38 women undergoing infertility work-up. Tubal transport demonstrated by RN-HSG was comparably distributed in both groups and classified as bilateral (17 versus 19), unilateral (12 versus 7) or no transport (6 versus 9). In each group three RN-HSG images were not interpretable. There was no association between patency test results and RN-HSG in the two groups. Our data suggest that RN-HSG in its present form does not seem to be a reliable method for infertility work-up. Because RN-HSG and patency tests most probably measure different properties of the genital tract, the phenomenon of active particle transportation should be studied further to enable the development of a reliable tool for the investigation of tubal function.
OBJECTIVES: To investigate the outcome of neo-adjuvant hormone treatment before radical prostatectomy regarding local tumour extension, peri-operative blood loss and operation time. PATIENTS: Of 111 surgically treated patients with prostate cancer (T1b-T3a, N0, M0, G1-3), 55 were randomised to immediate radical prostatectomy and 56 to 3 months of neo-adjuvant treatment with triptorelin (3.75 mg i.m. every 28 days) and cyproterone acetate (50 mg b.i.d. for 3 weeks to prevent flare). RESULTS: No differences were found in blood loss or operation time but patients who had neo-adjuvant treatment had a significantly lower frequency of positive margins (41 vs. 23%, p = 0.013). CONCLUSION: Neo-adjuvant treatment does not facilitate radical prostatectomy but may improve the chance of local cure. This must, however, be documented with long-term follow-up in randomised patients.
The C-terminus of alpha-spectrins contains two putative calcium-binding sites or EF-hands. To characterize the binding, we have isolated clones from a human fetal liver cDNA library and expressed several fragments comprising either one or both of these sites. When the isolated clones were sequenced, we found that three consecutive nucleotides differed compared to the published sequence. The discrepancy affected two codons in the first of the two putative calcium sites. These codons translated into glutamate and phenylalanine, which are identical to the residues present at the same position in other alpha-spectrins. In the presence of magnesium, only recombinant peptides comprising the second putative site bound calcium as determined by a calcium overlay assay. Although the first putative EF-hand appeared to bind some calcium in the absence of magnesium, no binding could be detected under stringent conditions. Therefore, it is likely that the second EF-hand constitutes the only functional calcium-binding site in the C-terminus of human non-erythroid alpha-spectrin. Since peptides comprising the second EF-hand bound calcium nearly as well as intact spectrin, it is also apparent that the second EF-hand constitutes the major binding site for calcium in spectrin. The relative change in negative ellipticity, induced by the binding of calcium, indicates a dissociation constant of approximately 120 microM.
Both brain and erythrocyte spectrin bound calmodulin in a calcium-dependent manner when immobilized on a polyvinylidene difluoride (PVDF) membrane, though the affinity of the non-erythroid spectrin was much greater than that of the erythroid isoform. The interaction was characterized further using equilibrium partition. In the presence of calcium, the partition behavior of calmodulin was affected by both spectrins, though brain spectrin caused a much larger change in partition. However, in both cases it was evident that the observed partition behavior of calmodulin was due to complex formation with spectrin. Analysis of the equilibrium partition data indicated the presence of a high-affinity site characterized by a dissociation constant of about 0.3 microM and probably one or more much weaker sites (> 0.3 mM). The presence of at least two distinct binding sites was substantiated by the observation that truncated recombinant spectrin fusion proteins comprising either the middle part or the C-terminal of non-erythroid alpha-spectrin bound calmodulin.