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Biomedical subjects

M Hellström

Publications and source records attributed to M Hellström.

At least 37 records · Page 2Linked to original sources

Long-term follow-up of reflux nephropathy in adults with vesicoureteral reflux--radiological and pathoanatomical analysis.

PURPOSE: To study the long-term development of urographic renal morphology in adults with vesicoureteral reflux, to investigate the relationship between renal damage and reflux grade, and to analyse the association between the long-term urographic outcome and the occurrence of acute pyelonephritis and reflux during follow-up. The purpose was also to try to distinguish between acquired and developmental renal damage, based on analyses of renal histological specimens and urographic features, and to analyse associated congenital urogenital abnormalities and family history of reflux, reflux nephropathy, urological malformation or death from end-stage renal disease. MATERIAL AND METHODS: Renal damage was identified in 100 (83 women) of 115 adults, selected because of documented reflux. Eighty-seven patients had two urographies done (median interval 14.3 years). The extent and progression of renal damage were assessed and features of developmental renal damage were determined. Histological renal specimens were available in 23 patients with renal damage. RESULTS AND CONCLUSIONS: The extent of renal damage correlated positively with the severity of reflux. No renal damage developed during the follow-up in 45 previously undamaged kidneys and progression of renal damage was rare (4 of 120 previously damaged kidneys), despite persisting reflux in half of the cases and episodes of acute pyelonephritis during follow-up. Thus, repeated renal imaging is rarely justified in adults with reflux nephropathy. Histological examination showed "chronic pyelonephritis" in all 23 cases and co-existing renal dysplasia in 1 case. The detailed urographic analysis did not reveal support for developmental renal damage. High frequencies of associated congenital urogenital abnormalities and of a positive family history were found. Thus, congenital and/or hereditary factors cannot be discarded as background factors for the development of renal damage.

Acute Disease↗

Conservative treatment and anti-reflux surgery in adults with vesico-ureteral reflux: effect on urinary-tract infections, renal function and loin pain in a long-term follow-up study.

STUDY PURPOSE: To investigate the long-term effects in adults of conservative treatment and anti-reflux surgery for vesico-ureteral reflux on urinary-tract infections, renal function, and loin pain. METHODS: Of 115 adult patients with vesico-ureteral reflux diagnosed between 1968 and 1984, conservative treatment was given to 46 patients (36 women) and anti-reflux surgery was performed in 57 patients (52 women). The remaining 12 patients underwent nephrectomy or heminephrectomy and were excluded from the study. The anti-reflux surgical methods used were the Politano-Leadbetter procedure in 44 patients (73 ureters) and the Hutch procedure in 19 patients (25 ureters). Six of these patients were operated on with both methods. RESULTS: The frequency of acute pyelonephritis was significantly reduced after anti-reflux surgery (P < 0.0001) as well as after diagnosis of vesico-ureteral reflux in the group given conservative treatment (P or < 0.001). The frequency of lower-urinary-tract infections was not altered in either group. Surgery had no effect on significant albuminuria (Albustix > or = 2+) or on progressive renal functional deterioration. Forty-three patients reported recurrent loin pain at the time of diagnosis or anti-reflux surgery. Only one of the 12 patients in the conservative group, compared with 29 of the 31 patients in the anti-reflux surgery group, obtained relief from loin pain during the follow-up. Nine patients in the anti-reflux surgery group reported restitution of reduced general well-being after surgery. These patients had experienced weariness and/or headache before surgery. Vesico-ureteral reflux was eliminated more frequently (P < 0.01) in the patients operated on by the Politano-Leadbetter procedure (94%) than in those operated on by the Hutch procedure (68%). CONCLUSIONS: Loin pain is common in adults with vesico-ureteral reflux and is effectively eliminated by anti-reflux surgery. Anti-reflux surgery should be considered in adults with vesico-ureteral reflux and very frequent acute pyelonephritic attacks only if conservative treatment has failed to alleviate these symptoms. Anti-reflux surgery is not indicated with the aim of arresting renal functional deterioration.

Adolescent↗

Association between urinary tract infection, renal damage and birth size.

UNLABELLED: The aim of this study was to investigate whether birth size is associated with permanent renal damage in children with urinary tract infection (UTI). A cohort of 1221 children under 16 y of age was diagnosed with their first symptomatic UTI between 1970 and 1979. Of these, 74 had urographic renal scarring in childhood and 57 were re-examined as adults. The birth files of 48 of these patients (35F, 13M) were available, and birthweight and birthlength in relation to gestational age were analysed and compared with a Swedish reference population. Children who had renal damage without vesicoureteric reflux were significantly smaller at birth (median weight, -0.76 SDS) compared with both children who had renal damage and reflux (median weight, -0.01 SDS) and the reference population. CONCLUSION: The demonstration of low birthweight among children with UTI and renal damage but no reflux suggests that low birthweight may be a risk factor for the development of renal damage.

Adolescent↗

[Risk of early therapeutic failure after prostatectomy is relatively great. Tumor grade and preoperative serum level of PSA are significant prognostic variables].

Prostate cancer is the most common malignancy among males in the West. Any reduction in mortality would require early detection of cases in which curative treatment is possible. From 1994 through 1998, 105 patients with clinically localised T1-T2 tumours were operated via radical prostatectomy at Karolinska sjukhuset in Stockholm. Three patients were lost to follow-up. We obtained clinical data from patients' records and used pathologist reviews to characterise tumours regarding grade and histopathological stage. We used PSA in serum as a surrogate endpoint, with a value above 0.6 ng/ml designated as treatment failure. Outcome was examined with respect to tumour grade, histopathological stage and pre-operative PSA level. Altogether 22% of patients showed PSA failure during follow-up. No mortality due to prostate cancer was recorded. We found that both tumour grade and pre-operative serum PSA level correlated well with treatment failure (P < 0.01). Our findings illustrate the diagnostic difficulties involved, since a relatively large percentage of patients were registered for treatment failure shortly after radical prostatectomy.

Follow-Up Studies↗

Exposure of the porcine spine to mechanical compression: differences in injury pattern between adolescents and adults.

Recent studies of the spine in adolescents who have sustained trauma have shown injuries to the growth zone, whereas injuries to the vertebral body have been described in other studies of only adults. There are also reports on different clinical signs and radiological findings in adolescents with lumbar disc herniation when compared to adults. In order to find an explanation for these differences between adolescents and adults, this experimental study was performed. Six cadaveric lumbar motion segments (vertebral body-disc-vertebral body) obtained from three young male pigs and six lumbar motion segments obtained from three mature male pigs were tested in axial compression to failure. All units were examined with plain radiography and magnetic resonance imaging before and after compression. After the compression, histological samples were taken from the injury site. In the adolescents, a fracture was consistently found in the endplate through the posterior part of the growth zone, displacing the anulus fibrosus with a bony fragment at the point of insertion to the vertebra. This type of injury could not be detected in any of the adults; instead, there was a fracture of the vertebra in four cases, and in two cases, a rupture of the anulus fibrosus without a bony fragment was seen. This study showed that, when compressed to failure, the weakest part of the lumbar spine of the adolescent pig differs from that of the mature pig in the same way that studies on human spinal units have shown.

Age Factors↗

PDGF-C is a new protease-activated ligand for the PDGF alpha-receptor.

Platelet-derived growth factors (PDGFs) are important in many types of mesenchymal cell. Here we identify a new PDGF, PDGF-C, which binds to and activates the PDGF alpha-receptor. PDGF-C is activated by proteolysis and induces proliferation of fibroblasts when overexpressed in transgenic mice. In situ hybridization analysis in the murine embryonic kidney shows preferential expression of PDGF-C messenger RNA in the metanephric mesenchyme during epithelial conversion. Analysis of kidneys lacking the PDGF alpha-receptor shows selective loss of mesenchymal cells adjacent to sites of expression of PDGF-C mRNA; this is not found in kidneys from animals lacking PDGF-A or both PDGF-A and PDGF-B, indicating that PDGF-C may have a unique function.

Animals↗

First Scandinavian experience of electrical sacral nerve stimulation in the treatment of the overactive bladder.

OBJECTIVE: This study aimed to evaluate the efficacy of electrical sacral nerve stimulation (SNS) in the treatment of urinary incontinence and urinary retention refractory to conservative treatment, and to assess the impact of urodynamic abnormalities and electrode position. MATERIAL AND METHODS: Thirty patients (10 men, 20 women) with a mean age of 59 years (range 21-79 years), all of whom had longstanding symptoms ranging from 2 to 46 years (mean 12.4 years), were subjected to a percutaneous test stimulation. Ten patients responded well, resulting in a permanent implant in nine patients. Electrode positions were determined by plain X-ray and computed tomography. RESULTS: Radiologically, a variety of positions of the temporary electrodes was seen. In the implanted patients, long-term symptom reduction varied over time, ranging from total relief to partial or total recurrence of symptoms. CONCLUSIONS: SNS is a new promising option for the treatment of urge incontinence. Refined instruments for proper patient selection and the optimal way to position the electrode remain to be developed.

Adult↗

Early myotome specification regulates PDGFA expression and axial skeleton development.

Reciprocal defects in signaling between the myotome and the sclerotome compartments of the somites in PDGFRalpha and Myf5 mutant embryos lead to alterations in the formation of the vertebrae and the ribs. To investigate the significance of these observations, we have examined the role of PDGF signaling in the developing somite. PDGFA ligand expression was not detected in the myotome of Myf5 null mutant embryos and PDGFA promoter activity was regulated by Myf5 in vitro. PDGFA stimulated chondrogenesis in somite micromass cultures as well as in embryos when PDGFA was knocked into the Myf5 locus, resulting in increased vertebral and rib development. PDGFA expression in the myotome was fully restored in embryos in which MyoD has been introduced at the Myf5 locus but to a lesser extent in similar myogenin knock-in embryos. These results underscore the importance of growth factor signaling within the developing somite and suggest an important role for myogenic determination factors in orchestrating normal development of the axial skeleton.

Alleles↗

Standardized ultrasound method for assessing detrusor muscle thickness in children.

PURPOSE: We standardized transabdominal ultrasound measurement of bladder wall thickness in children and evaluated its reliability. MATERIALS AND METHODS: Using ultrasonography we measured the thickness of the low echogenic layer of the ventral and dorsal bladder walls at increasing degrees of bladder fullness in the setting of voiding cystourethrography. For assessing intra-observer variability an observer blinded to the numerical values of the measurements studied 38 patients 0.2 to 13.7 years old (median age 1. 5). Measurements were performed as pairs of replicates at well-defined sites with reference to the urachal remnant, and rectal impression and/or contour. For assessing interobserver variability 3 independent observers measured the same child. Eight children 0.3 to 10.5 years old (median age 6.4) were evaluated at 2 degrees of bladder fullness per child. RESULTS: The thickness of the low echogenic layer of the ventral and dorsal walls was 0.4 to 2.9 (median 0.9) and 0.4 to 2.8 mm. (median 1.1). The dorsal wall was slightly thicker than the ventral wall. The intra-observer and interobserver variability of measurements (standard deviation) was 0. 2 mm. for each wall part. There was a small systematic difference among observers. CONCLUSIONS: It is possible to determine the thickness of the low echogenic layer of the bladder wall with a systematic and anatomically defined method of acceptably reliable measurements. The ventral and dorsal walls should continue to be measured until more is known about their pathological appearance.

Adolescent↗

PDGFB regulates the development of the labyrinthine layer of the mouse fetal placenta.

PDGFB is a growth factor which is vital for the completion of normal prenatal development. In this study, we report the phenotypic analysis of placentas from mouse conceptuses that lack a functional PDGFB or PDGFRbeta gene. Placentas of both types of mutant exhibit changes in the labyrinthine layer, including dilated embryonic blood vessels and reduced numbers of both pericytes and trophoblasts. These changes are seen from embryonic day (E) 13.5, which coincides with the upregulation of PDGFB mRNA levels in normal placentas. By E17, modifications in shape, size, and number of the fetal blood vessels in the mutant placentas cause an abnormal ratio of the surface areas between the fetal and the maternal blood vessels in the labyrinthine layer. Our data suggest that PDGFB acts locally to contribute to the development of the labyrinthine layer of the fetal placenta and the formation of a proper nutrient-waste exchange system during fetal development. We point out that the roles of PDGFB/Rbeta signaling in the placenta may be analogous to those in the developing kidney, by controlling pericytes in the labyrinthine layer and mesangial cells in the kidney.

Animals↗

Comparison of various D-dimer tests for the diagnosis of deep venous thrombosis.

Analyses of D-dimers in plasma are frequently used as diagnostic tools for deep venous thrombosis (DVT). Enzyme-linked immunosorbent assays (ELISAs) are considered to be the method of choice for quantitative assays, but are time consuming. Therefore, we have assessed plasma levels of D-dimers in patients with clinically suspected DVT using quantitative (Asserachrom D-Di ELISA and TintElize), semiquantitative (Minutex latex, D-Di latex, NycoCard D-Dimer) and qualitative (INSTANT.I.A) assays. Phlebography was used as the gold standard to verify or exclude the suspected diagnosis. We conclude that the fast assays, INSTANT.I.A and Minutex, have essentially the same negative predictive value [91% and 89%, respectively, using a cut-off value < 0.5 mg/l fibrinogen equivalent units (FEU)] for excluding DVT as the Asserachrom D-Di ELISA and TintElize tests (92%). The D-Di Latex assay had a negative predictive value of 82% (cut-off < 0.5 mg/l FEU) and turned out to be less useful in our material. The NycoCard D-dimer assay had a negative predictive value of 100% when using the cut-off value < 0.5 mg/l FEU, but this was substantially lower when the cut-off was changed to < or = 0.5 mg/l. Thus, we conclude that several fast tests offer a simpler and more rapid way of determining plasma levels of D-dimer than conventional ELISA methods without loss of clinical usefulness in excluding DVT.

Biological Assay↗

Diagnosis of vesico-ureteric reflux.

The demonstration and grading of reflux is crucial in examination and follow-up of any child with upper urinary tract infection. A variety of factors can influence the occurrence of reflux, e.g. race, genetics, state of maturation of the ureterovesical valve, diuresis, infection and bladder dysfunction, including obstruction and neurogenic disorders. Even when reflux is investigated under strictly standardized conditions, two consecutive bladder fillings frequently show different grades of reflux. Voiding cystourethrography is, to date, the only method with a generally accepted, well-defined grading of reflux. It also allows detection of intrarenal reflux and anatomical and functional information about the bladder and urethra that is unobtainable by other methods. It is therefore usually considered the method of choice. Radionuclide cystography and, possibly, contrast enhanced ultrasonography can be complementary to voiding cystourethrography, but mainly for postoperative follow-up and screening of siblings.

Chelating Agents↗

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.

Chelating Agents↗

Role of PDGF-B and PDGFR-beta in recruitment of vascular smooth muscle cells and pericytes during embryonic blood vessel formation in the mouse.

Development of a vascular system involves the assembly of two principal cell types - endothelial cells and vascular smooth muscle cells/pericytes (vSMC/PC) - into many different types of blood vessels. Most, if not all, vessels begin as endothelial tubes that subsequently acquire a vSMC/PC coating. We have previously shown that PDGF-B is critically involved in the recruitment of pericytes to brain capillaries and to the kidney glomerular capillary tuft. Here, we used desmin and alpha-smooth muscle actin (ASMA) as markers to analyze vSMC/PC development in PDGF-B-/- and PDGFR-beta-/- embryos. Both mutants showed a site-specific reduction of desmin-positive pericytes and ASMA-positive vSMC. We found that endothelial expression of PDGF-B was restricted to immature capillary endothelial cells and to the endothelium of growing arteries. BrdU labeling showed that PDGFR-beta-positive vSMC/PC progenitors normally proliferate at sites of endothelial PDGF-B expression. In PDGF-B-/- embryos, limb arterial vSMC showed a reduced BrdU-labeling index. This suggests a role of PDGF-B in vSMC/PC cell proliferation during vascular growth. Two modes of vSMC recruitment to newly formed vessels have previously been suggested: (1) de novo formation of vSMC by induction of undifferentiated perivascular mesenchymal cells, and (2) co-migration of vSMC from a preexisting pool of vSMC. Our data support both modes of vSMC/PC development and lead to a model in which PDGFR-beta-positive vSMC/PC progenitors initially form around certain vessels by PDGF-B-independent induction. Subsequent angiogenic sprouting and vessel enlargement involves PDGF-B-dependent vSMC/PC progenitor co-migration and proliferation, and/or PDGF-B-independent new induction of vSMC/PC, depending on tissue context.

Actins↗

Injuries in the adolescent porcine spine exposed to mechanical compression.

STUDY DESIGN: An experimental porcine study in which functional lumbar spinal units were tested in compression to failure. Biomechanical, radiographic, magnetic resonance imaging, and histological characteristics are described. OBJECTIVES: To explain the different patterns of injury seen in adults and adolescents resulting from traumatic injury to the vertebrae and to explain the mechanism behind traumatic displacement of the ring apophysis seen in athletes. SUMMARY OF BACKGROUND DATA: Recent investigations of the spine in adolescent who have sustained trauma have shown injuries to the growth zone, whereas studies of adults have shown injuries to the vertebral body. A higher frequency of abnormalities in the discs, the vertebral bodies, the endplates, and the ring apophyses has been demonstrated in athletes with high loads on the spine. There is controversy over the etiology of these changes. METHODS: Twelve functional lumbar spinal units (vertebra-disc-vertebra) obtained from six young male pigs were tested in compression to failure. All units were examined with plain radiography and magnetic resonance imaging before and after compression. After the compression, histologic samples were taken from the injury site. RESULTS: Identical traumatic changes were seen in all functional lumbar spinal units, i.e., fracture in the endplate through the growth zone posteriorly and displacement of the anulus fibrosus with a bony fragment at the point of insertion of the vertebra. The nucleus pulposus was ruptured and displaced through the fracture line in all cases. The injuries were not seen on radiographs but were detected on magnetic resonance images, as confirmed on microscopic and histologic examination. CONCLUSION: This study shows that the weakest part of the lumbar spine of the juvenile pig, when compressed, is the growth zone and the junction between the point of insertion of the anulus fibrosus and the vertebra. This location of weakness may explain the high frequency of disc degeneration and "persisting apophysis" seen in the spine of athletes.

Animals↗

Evaluation of DMSA scintigraphy and urography in assessing both acute and permanent renal damage in children.

PURPOSE: To evaluate dimercaptosuccinic acid (DMSA) scintigraphy and urography in the detection of renal involvement in children with urinary tract infection (UTI) in order to identify patients with a high risk of developing renal damage. MATERIAL AND METHODS: A total of 157 children (median age 0.4 years, range 5 days to 5.8 years) with first-time symptomatic UTI were examined scintigraphy (with an assessment of renal area involvement) and urography at the time of UTI and 1 year later. All evaluations were made blindly. RESULTS: Of the total 314 kidneys, 80 (25%) were abnormal at initial scintigraphy. Of these 80 kidneys, 44 (55%) had normalized at follow-up. Of the 234 initially normal kidneys, 29 (12%) were abnormal at follow-up. One year after UTI, abnormalities were seen in 59 children at scintigraphy and in 18 children at urography. Renal area involvement was larger and split function abnormalities more common in kidneys that were abnormal at both scintigraphy and urography than in kidneys with only scintigraphic abnormalities. CONCLUSION: Quantitation of renal area involvement and split renal function at early scintigraphy would seem to be useful in identifying patients at risk of developing renal damage. Urography at 1 year after infection identified mainly those with the most severe scintigraphic abnormalities. The clinical importance of scintigraphic abnormalities that are not confirmed by urography is not known.

Acute Disease↗

Endothelial-perivascular cell signaling in vascular development: lessons from knockout mice.

The importance of perivascular-endothelial cell interactions during blood vessel development is discussed in the light of recent findings in platelet-derived growth factor-B, platelet-derived growth factor receptor-beta, angiopoietin-1 and tie-2 knockout mice, which all show deficient development of perivascular cells. The initial formation of networks of endothelial tubes (vasculogenesis) does not seem to depend on the perivascular cells but subsequent vessel remodeling relies on mesenchymal-endothelial short-range signaling. Based on findings in platelet-derived growth factor and platelet-derived growth factor receptor knockout mice, a general model for the role of platelet-derived growth factors in smooth muscle development is proposed.

Angiopoietin-1↗