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Biomedical subjects

B Jacobsson

Publications and source records attributed to B Jacobsson.

At least 19 recordsLinked to original sources

Early 99mTc dimercaptosuccinic acid (DMSA) scintigraphy in symptomatic first-time urinary tract infection.

During a 2 year period, 175 children below 6 years of age (median 0.4 year) with non-obstructive symptomatic urinary tract infection were studied by 99mTc dimercaptosuccinic acid (DMSA) scintigraphy. DMSA scintigraphy was performed at a median of 10 days after the start of treatment and was abnormal in 73 children (42%), equivocal in 29 (16%) and normal in 73 (42%). Reflux was seen in 27% of all children and in 38% of the renal units that were abnormal at DMSA scintigraphy. A decreasing frequency of abnormalities at DMSA scintigraphy was seen within the first 14 days after the start of treatment. C-reactive protein and grade of reflux correlated significantly with abnormal DMSA studies. To demonstrate renal involvement in acute urinary tract infection, DMSA scintigraphy should be performed within days after the start of treatment. It is noteworthy that reflux was seen in less than half of renal units with abnormal DMSA scintigraphy.

Acute Disease

Clonal cell lineage involvement in myelodysplastic syndromes studied by fluorescence in situ hybridization and morphology.

We have used DNA fluorescence in situ hybridization (FISH) in combination with morphology to study cell lineage involvement in peripheral blood and bone marrow smears from 15 patients with myelodysplastic syndromes (MDS) and known numerical chromosomal aberrations. Eleven cases were investigated at diagnosis of MDS, and four at transformation to acute myeloid leukemia (MDS-AML). Using conventional cytogenetics, monosomy 7 was detected in nine cases, monosomy 17 in two, and trisomy 8 in five, either as a single aberration or as part of a complex clone. One case had both monosomy 7 and 17. Three biotinylated DNA probes directed against the pericentromeric region of chromosomes 7, 8 and 17, respectively, were used. Bone marrow smears were first stained with May-Grünewald-Giemsa (MGG) for morphologic evaluation, and regions of interest documented by photography. Later the same regions were targeted after hybridization, which allowed FISH analysis of selected bone marrow cells. In each patient between 267 and 921 cells (mean 453) were studied. In most cases a majority of the non-lymphoid bone marrow cells appeared to be of clonal origin, ie showed either monosomy or trisomy by FISH, while in contrast both lymphocytes and plasma cells generally were disomic, ie displayed two fluorescent spots for each probe. The percentages of clonal bone marrow cells differed greatly between patients, but in a single case there was a good agreement between the extent of granulocytic, monocytic and erythrocytic cell lineage involvement. In relation to the clinical stage of MDS, patients with more advanced disease had a significantly higher mean percentage of bone marrow blasts showing monosomy or trisomy, while disomic, possibly non-clonal cells were more frequent among the earlier forms of MDS. In the four cases of MDS-AML nearly all non-lymphoid bone marrow cells belonged to the abnormal clone. The FISH technique offers information regarding the distribution of clonal and non-clonal bone marrow cells in MDS, which might have prognostic and possibly, therapeutic implications.

Acute Disease

Decreased thymidine kinase levels in peripheral blood cells from HIV-seropositive individuals: implications for zidovudine metabolism.

Azidothymidine (zidovudine, AZT) used for treatment of HIV infection blocks the viral reverse transcriptase after phosphorylation by cellular enzymes. The first step in this reaction is the formation of AZT monophosphate, primarily catalyzed by host cytoplasmatic thymidine kinase (TK1). The activity of TK1 was determined in extracts of PHA-stimulated peripheral blood mononuclear cells (PBMCs) from 20 healthy volunteers and 49 HIV-infected patients at different stages of disease. In both groups we found a large intra- and interindividual variation of TK activity. Because TK1 expression is cell cycle regulated the proportion of stimulated cells was determined in the samples and the median thymidine kinase activity calculated. It was 3.0 pmol/mg/min x % S phase in the HIV-seronegative group and 1.1 pmol/mg/min x % S phase in HIV-infected individuals. The difference in thymidine kinase activity is statistically significant (p = 0.0001). The concentration of TK1 protein in the same extracts was also determined by immunoblotting. A positive correlation (r = 0.74) was observed between TK activity and amount of TK1 protein. The reason for this downregulation of TK is still unknown but may be related to the anergy observed in lymphocytes from HIV-infected persons. The reduced capacity for intracellular phosphorylation of AZT in HIV-infected individuals may be an important factor in the emergence of clinical AZT resistance and should also be accounted for in testing AZT resistance in vitro with PBMCs from healthy blood donors.

Antiviral Agents

Transthyretin and cystatin C are catabolized in proximal tubular epithelial cells and the proteins are not useful as markers for renal cell carcinomas.

Ten human kidney specimens and thirty-two renal cell carcinomas were investigated for the presence of transthyretin mRNA and cystatin C mRNA using Northern blot analysis. Five of ten kidney specimens and 15 of 32 renal carcinomas were also immunohistochemically investigated for the presence of the corresponding proteins. Transthyretin mRNA could not be detected in any of the normal or neoplastic tissue preparations, whereas low amounts of cystatin C mRNA were found in nine of ten normal kidneys and in 24 of 32 renal cell carcinomas. Immunoreactive transthyretin and cystatin C were present in proximal tubular epithelial cells of all kidney specimens, whereas neither of the proteins was detected the tumour cells of the renal carcinomas. Immunoreactive cystatin C was, however, demonstrated in scattered monocyte/macrophage-like cells. We conclude that the presence of immunoreactive transthyretin and cystatin C in proximal tubular cells of the kidney is most likely due to reabsorption of the proteins from the primary urine. The small amounts of cystatin C mRNA in some of the normal and neoplastic renal preparations are probably due to cystatin C synthesis in macrophages. Transthyretin has been recommended as an immunohistochemical marker for renal cell carcinomas. Our results, however, clearly indicate that neither transthyretin nor cystatin C constitutes a useful marker for such neoplasms.

Biomarkers, Tumor

Imaging of solid kidney tumours in children.

Eighteen children aged 6 months to 12 years with 20 solid renal tumours: 13 Wilms' tumours (WT), 2 clear cell sarcomas of the kidney, 1 malignant rhabdoid tumour of the kidney and 2 cases of bilateral nephroblastomatosis with Wilms' tumour underwent evaluation with US, CT and MR imaging. Contrast-enhanced CT and non-enhanced MR were equally accurate in determining the size and origin of the tumour but were unreliable in separation of stages I, II and III. US could only accurately assess the size of the tumours. MR characteristics varied somewhat between WTs and non-WTs but contrast-enhanced MR imaging might be useful for separation of WTs from nephroblastomatosis.

Child

Reliability of ultrasonography in identification of reflux nephropathy in children.

OBJECTIVE: To assess the ability of ultrasonography to identify reflux nephropathy in children after urinary tract infection. DESIGN: Ten experienced radiologists performed a total of 240 ultrasonographic examinations of kidneys in a one day study. The examiners were unaware of the results of previous radiological and clinical examinations and of the proportions of normal and abnormal kidneys. Urography was used as method of reference, supported by static renal scintigraphy (dimercaptosuccinic acid labelled with technetium-99m) in half of the cases. SETTING: Outpatient radiology department. SUBJECTS: 25 children aged 2-16 years (20 kidneys with and 30 kidneys without renal scarring). MAIN OUTCOME MEASURES: Renal scarring. Overall size and length of kidneys. Sensitivity and specificity including receiver operator characteristics and variation between observers. RESULTS: With renal scarring as the diagnostic criterion and including cases classified as abnormal, probably abnormal, and uncertain the sensitivity of ultrasonography was 54% (specificity 80%). Addition of reduced renal size as a diagnostic criterion increased the sensitivity to 64% (specificity 79%). There were, however, wide variations between observers, with sensitivity ranging between 40% and 90% (specificity 94% to 65%). CONCLUSIONS: Because of its low sensitivity and specificity and poor agreement between observers, ultrasonography cannot be generally recommended for the detection of reflux nephropathy after urinary tract infection in children.

Adolescent

Cystatin C in the human pancreas and gut: an immunohistochemical study of normal and neoplastic tissues.

The occurrence of immunoreactive cystatin C (CC) in normal and neoplastic cells of the human pancreas and gut was investigated using an indirect streptavidin-biotin method on formaldehyde-fixed and paraffin-embedded tissues. Virtually all pancreatic islet cells and many neuroendocrine cells throughout the gastrointestinal tract showed strong CC immunoreactivity and a granular cytoplasmic staining pattern. All 14 endocrine pancreatic tumours (insulinomas, glucagonomas, gastrinomas and non-producing tumours), as well as 16 of 17 gut carcinoid tumours, were also strongly CC immunoreactive. In addition, non-endocrine epithelial cells of pancreatic ducts and the gastrointestinal mucosa and 20 of the 24 adenocarcinomas from these sites showed weak CC immunoreactivity. Thus, CC cannot be used as a reliable immunohistochemical marker for endocrine gastro-entero-pancreatic tumours despite the fact that the protein is strongly expressed in a majority of such tumours.

Adenoma

Acute hydrops of the gallbladder in childhood.

Acute hydrops of the gallbladder (AHGB) is a rare paediatric disease being diagnosed with increased frequency due to its association with other illnesses and the availability of ultrasonography. The symptoms and signs of AHGB include abdominal pain, vomiting, abdominal mass and/or tenderness. As these clinical features mimic the more common surgical conditions such as acute appendicitis, intussusception and volvulus, some cases are still diagnosed only at laparotomy. Diagnosis is established by ultrasonography of the abdomen demonstrating normal biliary ducts and a distended gallbladder without calculi or congenital malformation. The aetiology of acute hydrops of the gallbladder is unknown but may be multifactorial. Treatment varies from non-operative management to surgical intervention.

Acute Disease

Piroxicam and indomethacin suppositories for painful coxarthrosis.

Six orthopaedic clinics in Sweden made a comparison of the effects and side effects of Piroxicam (20 mg) and Indomethacin (100 mg) suppositories in 261 patients with painful coxarthrosis on the waiting list for total hip replacement (THR). The study was designed as a single blind study over 4 weeks. Amount of pain and range of motion was registered before the trial and compared with findings after 4 weeks, including reported side effects. Both drugs gave satisfactory pain relief without any appreciable variation on weightbearing or at rest. On the other hand, the trial showed a significant difference (p = 0.0033, Student's-test) between the two drugs as regards the frequency of side effects from the lower gastrointestinal tract, where piroxicam had a lower rate compared with indomethacin. No serious complications occurred; 16 patients dropped out, 8 in each group.

Aged

Eosinophilic bodies in pyloric and Brunner's gland cells.

A previously unreported cell phenotype occurred in the pyloric and Brunner glands in two gastrectomy specimens. The cells were characterised by homogeneous, eosinophilic material in the cytoplasm. The eosinophilic material had an abnormally strong reactivity for Cystatin C, a protein found recently in the normal secretion of pyloric and Brunner's gland cells. The reason for the apparent cytoplasmic accumulation of cystatin C in the two patients described remains unclear.

Brunner Glands

Intrauterine fetal death due to echovirus 11.

In a case of intrauterine fetal death in the 29th week of gestation, echovirus 11 could be isolated from the umbilical cord of the fetus. The mother had no apparent signs of infection but serological evidence of current echovirus 11 infection. Enterovirus PCR performed on paraffin-embedded specimens of various tissues (myocardium, lung, liver and placenta) from the fetus yielded positive results in all cases. These findings, together with supporting serological and epidemiological findings--e.g. proven echovirus 11 infection 3 weeks before in the 18-month-old son of the woman--constituted strong evidence that echovirus 11 infection was responsible for the fetal death.

Adult

Epidemiology of pelvic fractures in a Swedish county.

Epidemiologic features of pelvic fractures from 1976 to 1985 inclusive were studied in Skaraborg County, southwestern Sweden. The county had an average population of 269,000 inhabitants. During the 10-year period, 541 patients with pelvic fractures were treated in the hospital, and the incidence was 20 per 100,000. The incidence increased in the elderly, especially among women. Severe trauma dominated in age groups below 60 years, whereas moderate trauma dominated in older age groups. 81 percent were stable fractures of the pubic rami and 10 percent acetabular fractures. Associated injuries occurred in 21 percent of the patients, predominantly in those with severe trauma. The mean length of hospitalization was 3 weeks irrespective of whether or not the trauma was moderate or severe.

Adolescent

Intracellular metabolism of 3'-azidothymidine in isolated human peripheral blood mononuclear cells.

Azidothymidine (AZT) inhibits the replication of human immunodeficiency virus and it is the only drug so far licensed for treatment of acquired immunodeficiency syndrome (AIDS). A prerequisite for its antiviral activity is phosphorylation by cellular nucleoside kinases to the mono-, di-, and triphosphate levels. This study determined the capacity of isolated peripheral blood mononuclear cells (PBMC), resting or mitogen stimulated, from 36 different people of whom 5 were HIV+, to phosphorylate and accumulate intracellular AZT nucleotides. We found a large variation in the amount of products formed between PBMC treated at different times from the same individual as well as between the PBMC from different individuals. Resting PBMC showed the largest interindividual variation and their levels of AZT nucleotides were about 60-150-fold lower than in activated PBMC. The intracellular half lives of azidothymidine mono-, di-, and triphosphates, constituting, on the average, 96-99.2, 0.7-1.8, and 0.4-2.7% of total nucleotides at 0.08-1.6 microM AZT, respectively, were also determined. In mitogen-stimulated PBMC it was approximately 2.5 +/- 0.6 h for all the azidothymidine metabolites. The half-life for intracellular azidothymidine monophosphate in resting PBMC from two individuals was determined to 1.5 +/- 0.2 h. There appeared to be no significant difference in the AZT metabolism in PBMC from HIV-positive or-negative persons. A relative decrease in the intracellular formation of AZTDP and AZTTP from AZTMP was observed at concentrations of AZTMP above 1 microM. This fact may explain why lowering the doses of AZT still gives therapeutically efficient levels of the active metabolite AZTTP.

Adult

Disc degeneration and associated abnormalities of the spine in elite gymnasts. A magnetic resonance imaging study.

The thoracolumbar spine was examined by magnetic resonance imaging (MRI) and the history of back pain was analyzed in 24 male elite gymnasts (age range, 19-29 years) and in 16 male nonathletes (age range, 23-36 years). Disc degeneration, defined as reduced disc signal intensity, was significantly more common in athletes (75%) than in nonathletes (31%). The gymnasts also had a higher incidence of other abnormalities of the thoracolumbar spine, and there was a significant correlation between reduced disc signal intensity and the other abnormalities among the gymnasts. There were also significant correlations between back pain and reduced disc signal intensity and abnormal vertebral configuration when the gymnasts run a high risk of developing severe abnormalities of the thoracolumbar spine, and they often have a history of back pain.

Adult

Percutaneous nephrolithotomy through an intercostal approach.

During a 5-year period percutaneous nephrolithotripsy through an intercostal space was performed in 56 of 231 procedures. Minimal thoracic complications were seen in 3 of 53 patients with 11th intercostal space tracts into a lower, middle, or upper pole calyx. A working sheath and a pyelostomy drainage catheter were used in all these cases. Hydro- and pneumothorax requiring treatment occurred in 2 of 3 patients with a 10th intercostal space approach into an upper pole calyx combined with improper use of the working sheath and/or the pyelostomy catheter. Review of the literature also indicates that an intercostal approach appears safe when performed via the 11th intercostal space into a lower or middle pole calyx. Thoracic complications occurred when punctures were made towards an upper pole calyx or above the 11th rib. The complications may be limited by identifying the posterior inferior lung border by fluoroscopy during puncture, and performing it under general anesthesia with controlled breath-holding. The use of a working sheath to seal the pleural opening during the procedure and an efficient pyelostomy drainage catheter to allow free drainage of urine and to tamponade the tract postoperatively are also recommended.

Adult