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Biomedical subjects

B Sandstedt

Publications and source records attributed to B Sandstedt.

At least 37 records · Page 2Linked to original sources

Patients with implantable cardioverter-defibrillators and their conceptions of the life situation: a qualitative analysis.

The implantable cardioverter-defibrillator (ICD) is today widely used for the treatment of sudden cardiac near-death episodes as a result of malignant ventricular dysrhythmia. After examining the literature, only four descriptive studies, all carried out in the USA, with a qualitative analysis based on ICD-patients' own perspectives on their life situation have been found. The aim of this study was to describe how patients living with an ICD-device in south-western Sweden conceive their life situation. As the focus was on patients' conceptions seen from a holistic perspective, an analysis inspired by phenomenography was employed on a strategic sample of 15 ICD-patients. Six categories emerged: a feeling of safety, a feeling of gratitude, a feeling of being, having a network, having a belief in the future, and gaining awareness. Although the findings cannot be generalized because of the descriptive research design, they illuminate the beneficial as well as intrusive effects of such a device, and emphasize the need for support groups for patients and families as well as further education for personnel in hospital and primary health care.

Adaptation, Psychological↗

Altered expression of members of the IGF-axis in hepatoblastomas.

Previous reports have demonstrated that expression of insulin-like growth factor 2 (IGF2) is altered in hepatoblastoma. Using RNAase protection analysis (RPA), we examined the gene expression for IGF1, IGF2, IGF1R, M6P/IGF2R, IGFBP-1 and IGFBP-2 in a series of hepatoblastomas with corresponding normal liver from the same individuals. The results show that the expression of the IGF-axis members included in the present study are altered between tumour and normal, and indicate that the IGF-axis may be involved in hepatoblastoma development.

Genes, Tumor Suppressor↗

Local short-chain fatty acids supplementation without beneficial effect on inflammation in excluded rectum.

BACKGROUND: Rectal instillation of short-chain fatty acids (SCFA), important nutrients for the colorectal mucosa, has been suggested to be of therapeutic value in distal intestinal inflammation. METHODS: In this study nine patients with Hartmann-closed rectum after colectomy for acute colitis were investigated. In a double-blind crossover trial an enema containing SCFA or a placebo solution was administered twice daily for 3 weeks. Before entry into the protocol, after each treatment period, and 6 weeks after the study period the patients' symptoms were evaluated, rectal endoscopy was performed, histologic samples were scored, and microbiologic analyses were carried out. RESULTS: No significant differences in symptoms, in mucosal inflammation, in histologic scoring, or in microbiologic studies were found between SCFA and placebo periods. Unexpectedly, all but one patient entirely lacked coliform bacteria in the rectum. CONCLUSIONS: In this study SCFA enemas had no beneficial effect on inflammation in excluded rectum in patients earlier submitted to colectomy for colitis. However, a different rectal flora was detected in these patients.

Adult↗

Spectral turbulence and late potentials in the signal-averaged electrocardiograms of patients with monomorphic ventricular tachycardia versus resuscitated ventricular fibrillation.

Signal-averaged electrocardiograms (SAECG) were analyzed for late potentials and spectral turbulence in 208 patients with ischemic heart disease with a history of sustained monomorphic ventricular tachycardia (MVT) (n = 62), resuscitation from ventricular fibrillation (VF) (n = 64) or no ventricular tachyarrhythmia (n = 82). Receiver operating characteristic curves were utilized to optimize cut-off values for prediction of MVT and VF. Patients with MVT had a lower ejection fraction (mean = 0.37) than patients with VF (0.44; p = 0.01) and controls (0.48; p < 0.0001). The mean FQRSD in MVT patients (126 ms) was longer than in VF and controls (113 ms; p = 0.005 and 102 ms; p < 0.0001, respectively). The RMS40 was lower in MVT (19 microV) than in VF and controls (29 microV; p = 0.0003 and 28 microV; p < 0.0001, respectively); 81% of the MVT patients were spectral turbulence-positive vs 47% of VF patients and 31% of control patients (p < 0.0001 for both differences). With optimized reference values, FQRSD, TQRSD and ISCSD contributed significantly to the identification of MVT patients and FQRSD to VF patients. The sensitivity of combined time-domain and spectral turbulence analysis was 90% for MVT and 58% for VF, with 63% specificity. MVT patients had a lower ejection fraction and were more often late potential and spectral turbulence positive than VF and control patients. These findings indicate that a large electroanatomic substrate is required in MVT. A long FQRSD was a risk marker for both MVT and VF. Spectral turbulence analysis added independent information, and the combination of time-domain and spectral turbulence analysis was superior to either method alone in identifying the MVT patients. Neither method of analysis, singly nor in combination, performed satisfactorily in identification of VF risk.

Aged↗

Bladder cancer: allelic deletions at and around the retinoblastoma tumor suppressor gene in relation to stage and grade.

Inhibition of the retinoblastoma tumor suppressor gene (RB) is probably important in the pathogenesis of urinary bladder cancer. Little information is available concerning allelic loss on 13q11 to 13q32 and its relation to grade and stage. In a population-based study, freshly frozen tissue was collected from all new cases of urinary bladder cancer in the Stockholm region during 1995-1996. Here we report the occurrence of loss of heterozygosity (LOH) at seven sites in 13q11 to 13q32 as analyzed in 236 cases by a fluorescent multiplex PCR-based on tumor DNA and peripheral blood. For each site, about 30% of the cases were not informative because of homozygosity. Replication errors were detected in 4% (17 cases). LOH was found in 21 (at 13q11-12.1) to 32% (at 13q14.3 in RB) of the informative cases. A correlation was found between the prevalence of LOH at all observed loci and stage and grade, respectively, and it was statistically significant for 13q14.3. LOH at RB was found in Ta as well as grade 1 tumors. Also, a statistically significant correlation was found between the number of loci with LOH at 13q and tumor stage and grade, respectively. Typically an altered RB function is related to the expected clinical course of urinary bladder cancer, but allelic loss including the gene also occurs in low grade and low stage tumors. An altered RB function probably is not necessary for a malignant transformation of urothelial cells. The causal direction of the relation between the quantity of the deleted DNA and tumor aggressiveness is not clear.

Alleles↗

Expression of genes involved with cell cycle control, cell growth and chromatin modification are altered in hepatoblastomas.

Hepatoblastoma is a rare pediatric liver tumor. While much progress has been made in the treatment of the disease, very little is known about the moleculer events underlying the pathogenesis of this disease. We sought to investigate a series of hepatoblastomas for alterations in gene expression patterns with emphasis on important cell regulatory genes, including chromatin modifying enzymes, cyclin dependent kinase inhibitors, growth factors, oncogenes and cell cycle regulators. Total RNA was extracted from a series of sporadic hepatoblastomas with matched normal liver, some unmatched tumors and fetal livers, and gene expression was measured for various genes using RNase Protection Analysis (RPA). The results of this analysis show that the expression of many important regulatory genes are distinctly altered in these tumors, and a subset of tumors can be distinguished on the basis of these gene expression differences and histopathological features. Because the molecular events underlying the pathogenesis of this rare tumor are so poorly understood, this study represents a first step in determining some of the possible mechanisms involved which may provide future avenues of research.

Case-Control Studies↗

Pretreatment, ultrasound-guided cutting needle biopsies in childhood renal tumors.

BACKGROUND: The current International Society of Paediatric Oncology (SIOP)-10 protocol does not allow pretreatment histological classification of low-stage renal tumors in children for fear of needle tract recurrences. The aims of this retrospective study were to evaluate the safety, sensitivity, and specificity of ultrasound-guided cutting needle biopsies (UCNB) performed at our institution in pediatric patients with renal tumors. PROCEDURE: Of 28 pediatric patients presenting with a renal tumor between 1988 and 1996, 25 underwent biopsy with the Biopty biopsy instrument (needle diameter 1.2 mm). The preoperative biopsy and nephrectomy slides were reviewed by a SIOP reference pathologist. The patients' hospital records were reviewed and biopsy complications were noted. RESULTS: At review of the nephrectomy slides, the diagnoses were: Wilms tumor (16 patients), with anaplasia in one case, rhabdoid tumor (2 patients), neuroblastoma (2 patients), mesoblastic nephroma (2 patients), clear cell sarcoma (1 patient), malignant teratoma (1 patient), and renal cell carcinoma (1 patient). No needle tract recurrence or other major complication was observed. The only complication was local pain at the biopsy site, which occurred in 24% (6/25) of the cases. The sensitivity of UCNB was 76% (19/25); five biopsies did not yield diagnostic material and one was not concordant. All cases of Wilms tumor were correctly diagnosed by UCNB, but only 33% (3/9) of the other tumors. CONCLUSIONS: In all cases of Wilms tumor a correct diagnosis was made. The overall sensitivity was 76%. UCNB proved to be a safe procedure that was not associated with needle tract recurrence or other serious complications.

Adolescent↗

New definitions of focal and diffuse anaplasia in Wilms tumor: the International Society of Paediatric Oncology (SIOP) experience.

BACKGROUND: Unlike the original definitions of focal (FA) and diffuse anaplasia (DA) in Wilms tumor (WT), recently redefined FA and DA proved to be of prognostic significance. The aim of the study was to analyze WT from the SIOP file, the majority of which were treated with preoperative chemotherapy, in order to investigate whether chemotherapy influenced the presence of anaplasia, whether the new definitions were applicable to these tumors, and whether they were of prognostic significance. PROCEDURE: The unilateral anaplastic WT of children up to 16 years of age from the SIOP 6 and 9 nephroblastoma trials and studies were first classified according to the original definitions and analyzed. Then they were reclassified and analyzed according to the new definitions. RESULTS: Anaplasia was diagnosed in 86 (5.5%) of 1,554 unilateral WT. The age at diagnosis ranged from 9 to 175 months (median, 63) and more than half of children were over 5 years of age. From 15% to 85% of the tumor mass showed chemotherapy-induced changes. Blastemal anaplasia was seen in 74, stromal in 23, and epithelial in 22 cases. According to the original definitions, FA was diagnosed in 55 (64%) and DA in 31 (36%) cases. In total, 48% children were alive and well, including 53% with FA and 39% with DA (P = 0.23). When reclassified, 39 old FA cases were moved to the new DA group, resulting in 70 (81%) DA and 16 (19%) FA cases. The female-to-male ratio for FA changed from 1.9:1 to 1:1 while remained unchanged for DA. The percentage of FA stage I cases increased from 31% to 44%, while it decreased from 25% to 6% for stage III. For other stages it remained virtually unchanged. The overall 4-year actual survival was 75% for FA and 41% for DA (P = 0.03). CONCLUSIONS: Preoperative chemotherapy did not obliterate or produce anaplasia. The new definitions were applicable to pretreated cases and they were of prognostic significance.

Adolescent↗

Mammalian suppressor-of-fused modulates nuclear-cytoplasmic shuttling of Gli-1.

Sonic hedgehog, Patched and Gli are components of a mammalian signalling pathway that has been conserved during evolution and which has a central role in the control of pattern formation and cellular proliferation during development. Here we identify the human Suppressor-of-Fused (SUFUH) complementary DNA and show that the gene product interacts physically with the transcriptional effector GLI-1, can sequester GLI-1 in the cytoplasm, but can also interact with GLI-1 on DNA. Functionally, SUFUH inhibits transcriptional activation by GLI-1, as well as osteogenic differentiation in response to signalling from Sonic hedgehog. Localization of GLI-1 is influenced by the presence of a nuclear-export signal, and GLI-1 becomes constitutively nuclear when this signal is mutated or nuclear export is inhibited. These results show that SUFUH is a conserved negative regulator of GLI-1 signalling that may affect nuclear-cytoplasmic shuttling of GLI-1 or the activity of GLI-1 in the nucleus and thereby modulate cellular responses.

Adult↗

Helicobacter pylori gastritis in children: efficacy of 2 weeks of treatment with clarithromycin, amoxicillin and omeprazole.

Thirty-eight children with Helicobacter pylori gastritis diagnosed by histopathology, and/or bacteriological culture were treated with omeprazole, amoxicillin and clarithromycin. Follow-up endoscopy was performed in 34 children. Outcome was measured by negative histology and culture for H. pylori. Six patients were excluded. Of the 32 remaining children eradication was achieved in 75% (95% confidence interval 60-90%).

Adolescent↗

The human cationic antimicrobial protein (hCAP18), a peptide antibiotic, is widely expressed in human squamous epithelia and colocalizes with interleukin-6.

Peptide antibiotics are widespread in nature and, by providing a rapid first line of defense, may be key players in the innate immune system. Although epithelia are the main barriers shielding the internal environment from microorganisms, the role for peptide antibiotics in epithelial protection is unclear. We recently reported that the human cationic antimicrobial protein hCAP18, the precursor of the antimicrobial peptide called LL-37, is not expressed by normal human keratinocytes but is induced in various inflammatory skin disorders. In the present study we demonstrate that hCAP18 is consistently expressed at both mRNA and protein levels in squamous epithelia of the mouth, tongue, esophagus, cervix, and vagina in humans. The gene for hCAP18 contains promoter elements that are potentially regulated by interleukin-6, and our data further show a colocalization between interleukin-6 and hCAP18 expression in these tissues. Our finding that hCAP18 is widely produced in squamous epithelia suggests a role for this peptide in epithelial antimicrobial defense. Furthermore, colocalization with interleukin-6 indicates a potential local mechanism for the upregulation of hCAP18 at the epithelial surfaces.

Anti-Bacterial Agents↗

The role of preoperative chemotherapy in the treatment of nephroblastoma: the SIOP experience. Societe Internationale d'Oncologie Pediatrique.

Treatment of Wilms' tumor is an example of success of modern oncology. A combination of surgery, radiotherapy, and chemotherapy is widely accepted as the efficacious treatment of nephroblastoma. However, timing of each part of the treatment differs, in various protocols: the Societe Internationale d'Oncologie Pediatrique (SIOP) recommends the diagnosis based on imaging and metabolic exclusion of neuroblastoma to reduce the biopsy-related risk of spillage. In patients more than 6 months old, the treatment starts with the preoperative chemotherapy to improve the stage distribution at surgery and decrease the complications rate. Patients with advanced nephroblastoma, as those with vena cava thrombus and lung metastases, can benefit the most from the pretreatment. Results from the SIOP studies 6 and 9 confirm these statements: the stage distribution after the pretreatment reveals more than 50% of cases staged I, the 4-year disease-free survival in pulmonary stages IV was 83%, and of 42 patients with vena cava thrombus still present at surgery, 38 are alive from 27 to 109 months.

Child↗

The basic helix-loop-helix transcription factor dHAND, a marker gene for the developing human sympathetic nervous system, is expressed in both high- and low-stage neuroblastomas.

Neuroblastoma is derived from the sympathetic nervous system and might arise as a result of impaired differentiation, retaining the neuroblastic tumor cells in the cell cycle. Thus, to understand the genesis of neuroblastoma, the study of mechanisms and genes regulating normal sympathetic development is of potential interest. The basic helix-loop-helix transcription factors human achaete-scute homolog-1 (HASH-1) and deciduum, heart, autonomic nervous system, and neural crest derivatives (dHAND) are expressed in the sympathetic nervous system of embryonic mice and chicken, with undetectable postnatal expression. By in situ hybridization technique, we show that dHAND was expressed by human sympathetic neuronal and extra-adrenal chromaffin cells throughout embryonic and fetal life, and was initially expressed in immature chromaffin cells of the adrenal gland. With overt chromaffin differentiation, dHAND was down-regulated. HASH-1, in contrast, was expressed in human sympathetic cells only at the earliest embryonic ages examined (Week 6.5 to 7). All examined neuroblastoma specimens (25/25) and all cell lines (5/5) had detectable dHAND mRNA levels. HASH-1 expression in tumor specimens was more restricted, although all cell lines (5/5) were HASH-1-positive. These results show that neuroblastoma tumors have retained embryonic features, suggesting that many neuroblastomas are blocked at an early stage of normal development when HASH-1 and dHAND are expressed. dHAND also appears to be a reliable and potentially useful clinical diagnostic marker for neuroblastoma, because expression was not dependent on tumor or differentiation stages and other pediatric tumors were dHAND-negative.

Animals↗

Promoter-specific methylation and expression alterations of igf2 and h19 are involved in human hepatoblastoma.

In earlier studies we found up-regulation of promoter P3 transcription and total igf2 expression with concomitant down-regulation of h19 expression in human hepatoblastoma (HB). In this study, we investigated the methylation status of these 2 genes and their abnormal regulation in 7 hepatoblastomas and 5 normal counterpart tissues. A specific part of the P3 region of igf2 was de-methylated in tumors with up-regulation of the promoter activity. A site-specific DNA hypermethylation in the h19 5'-region was found in tumor tissues with concomitant down-regulation of this gene. Therefore, abnormal methylation was found to be correlated with altered regulation of igf2 and h19 expression in human hepatoblastoma and may be involved in the genesis of this tumor.

DNA Methylation↗

Virulence and colonization-associated properties of Helicobacter pylori isolated from children and adolescents.

Helicobacter pylori isolates from 32 children and adolescents were characterized with respect to putative virulence and colonization-associated properties. Only 3 of the subjects had duodenal ulcer. All but 2 of the remaining 29 had various degrees of chronic gastric inflammation. No significant correlation between degree of inflammation and presence of the cag-pathogenicity island, cytotoxin production, vacA alleles associated with cytotoxin expression, and binding ability to the Lewis(b) (Le[b]) oligosaccharide was found. Only 4 isolates expressed the Le(b)-specific adhesin, of which 3 were also cag region-positive. This is in contrast to adults with gastritis or peptic ulcer disease (or both), in whom most of the H. pylori isolates bind Le(b). In an in situ binding assay H. pylori were less able to adhere to gastric surface mucous cells in biopsies taken from children compared with adults, suggesting a lower expression of the Le(b) oligosaccharide in the children.

Adolescent↗

Short- and long-term performance of a tripolar down-sized single lead for implantable cardioverter defibrillator treatment: a randomized prospective European multicenter study. European Endotak DSP Investigator Group.

A new, thinner (10 Fr) and more flexible, single-pass transvenous endocardial ICD lead, Endotak DSP, was compared with a conventional lead, Endotak C, as a control in a prospective randomized multicenter study in combination with a nonactive can ICD. A total of 123 patients were enrolled, 55 of whom received a down-sized DSP lead. Lead-alone configuration was successfully implanted in 95% of the DSP patients vs 88% in the control group. The mean defibrillation threshold (DFT) was determined by means of a step-down protocol, and was identical in the two groups, 10.5 +/- 4.8 J in the DSP group versus 10.5 +/- 4.8 J in the control group. At implantation, the DSP mean pacing threshold was lower, 0.51 +/- 0.18 V versus 0.62 +/- 0.35 V (p < 0.05) in the control group, and the mean pacing impedance higher, 594 +/- 110 omega vs 523 +/- 135 omega (p < 0.05). During the follow-up period, the statistically significant difference in thresholds disappeared, while the difference in impedance remained. Tachyarrhythmia treatment by shock or antitachycardia pacing (ATP) was delivered in 53% and 41%, respectively, of the patients with a 100% success rate. In the DSP group, all 28 episodes of polymorphic ventricular tachycardia or ventricular fibrillation were converted by the first shock as compared to 57 of 69 episodes (83%) in the control group (p < 0.05). Monomorphic ventricular tachycardias were terminated by ATP alone in 96% versus 94%. Lead related problems were minor and observed in 5% and 7%, respectively. In summary, both leads were safe and efficacious in the detection and treatment of ventricular tachyarrhythmias. There were no differences between the DSP and control groups regarding short- or long-term lead related complications.

Adult↗

Pediatric rhabdomyosarcomas express the intermediate filament nestin.

Previous findings that the intermediate filament nestin is expressed in immature skeletal muscle cells prompted us to compare the staining patterns of nestin and desmin in rhabdomyosarcomas (RMSs) and in other small cell tumors of infancy. We found that nestin immunoreactivity was present in all of 29 examined typical RMSs, which also expressed desmin. Two undifferentiated tumors, primarily suspected to be RMSs, expressed nestin, but not desmin. One of these nestin-positive, desmin-negative tumors was positive for the expression of the myogenic regulatory gene MyoD and is considered to represent an undifferentiated RMS. The other, a paratesticular tumor, did not contain transcripts for MyoD, and most likely does not represent a RMS. In several RMSs and nonmuscle tumors, a z-disc-associated nestin immunoreactivity occurred as a paramalignant phenomenon in cross-striated muscle fibers adjacent to the tumor cells. Our findings indicate that nestin, although present also in tumors of the central and peripheral nervous systems, as well as in endothelial cells and in some muscle cells adjacent to tumors, is a useful complementary marker for RMS, particularly in very undifferentiated desmin-negative tumors.

Adult↗