Biomedical subjects

E Wilander

Publications and source records attributed to E Wilander.

At least 55 records · Page 3Linked to original sources

PubMed1997

Expression of islet amyloid polypeptide in fetal and adult porcine and human pancreatic islet cells.

The synthesis and intracellular localization of the putative hormone islet amyloid polypeptide (IAPP) and its relation to insulin and glucagon during ontogenesis was investigated in fetal and adult porcine and human pancreatic islets. By means of ultrastructural immunogold immunocytochemistry, it was revealed that IAPP is produced by the hormonally pluripotent endocrine stem cells from the earliest time point studied. IAPP was colocalized with insulin and glucagon in the immature and nondifferentiated cell granules in both species. In adult man, highly intense IAPP immunoreactivity was found in beta-cell granules and, at lower intensity, in delta-cell granules. Some alpha-cells also contained a small amount of IAPP in their granules, and among these occasional granules displayed an intense immunoreactivity. In adult pig, IAPP was stored in quantity in beta-cell granules and in small amounts in granules of alpha- and delta-cells. It was difficult to determine the presence of IAPP in pancreatic polypeptide cells, because they were so seldom seen in this material. It is concluded that, in both man and pig, fetal pancreatic islet stem cells synthesize and store IAPP together with insulin and glucagon. The storage in different types of cells and granules was not as predictable as that of the classical islet hormones. The substance is more widely distributed within the pancreatic islet cell types than are any of the other islet hormones, which presumably has functional implications.

Adult↗

PubMed1996

Detection of human papillomavirus in cervical intra-epithelial neoplasia, using in situ hybridization and various polymerase chain reaction techniques.

One hundred and forty-eight randomly chosen neutral-buffered formaldehyde-fixed cervical biopsies in which cervical intra-epithelial neoplasia (CIN) I-III had been diagnosed were tested for HPV (human papilloma virus) DNA by in situ hybridization (ISH) and polymerase chain reaction (PCR). For ISH, we utilized a biotinylated panprobe and type-specific, genomic probe sets. For PCR, we used the general primers GP5/GP6 and their recently described, elongated version GP5+/GP6+, and included the modification of hot-start PCR. Amplified DNA was detected by gel electrophoresis and slot blot hybridization. The positivity rate of ISH was 59% for all biopsies and 69%, 62% and 46% for CIN I, II and III, respectively. The sensitivity of GP5/GP6 was 74% with cold-start PCR and 78% with hot-start PCR. When GP5+/GP6+ was used, the sensitivity increased to 89% with cold-start PCR and to 95% with hot-start PCR. Based on the most sensitive PCR technique, HPV detection was 93%, 95% and 96% in CIN I, II and III, respectively. The number of HPV types decreased with the severity of the lesion, and HPV 16 was the predominant type. Multiple HPVs were rare and almost all HPV-positive cases could be typed. ISH and slot blot hybridization correlated well regarding HPV typing specificity. Our results confirm that distinct HPV types are present in a high proportion of cases of CIN. The sensitivity of ISH is lower than that of PCR. Furthermore, the modified general primers GP5+/GP6+ give a higher yield than GP5/GP6, while hot-start PCR increases sensitivity even further.

Adolescent↗

PubMed1996

Efficiency of percutaneous core biopsy in pancreatic tumor diagnosis.

BACKGROUND: Radiologic diagnosis of pancreatic tumors exhibits limited precision. The aim of this study was to investigate the outcome and complications of pancreatic core biopsy in patients with suspected pancreatic neoplasms. METHODS: One hundred patients underwent ultrasonography-guided core biopsy of 1.2 mm external diameter. Medical charts were examined for biochemical and clinical signs of complications. Final diagnosis was settled by operation, autopsy, and clinical signs of the disease including survival with at least 2.3 years of follow-up. RESULTS: Histopathologic biopsy evaluation showed correct discrimination between exocrine and endocrine tumors and nonneoplastic conditions in 89 patients. No false-positive cancer diagnosis was found, and guidance on nature of primary tumors was obtained for eight of eight metastases. The sensitivity was 91% for exocrine and 87% for endocrine pancreatic tumors, and negative predictive values of these diagnoses were 83% and 97%, respectively. No clinically significant complications were noted. CONCLUSIONS: Core biopsy is an attractive alternative to diagnostic laparotomy in unresectable pancreatic cancer and efficiently provides diagnosis of endocrine tumors and pancreatic metastases in conjunction with rare complications. Benign biopsy findings cannot be used to exclude presence of primary or metastatic pancreatic neoplasms.

Biopsy↗

PubMed1996

Two consensus primer systems and nested polymerase chain reaction for human papillomavirus detection in cervical biopsies: A study of sensitivity.

Polymerase chain reaction (PCR) is being increasingly used in clinical laboratories for the diagnosis of human papillomavirus. From the L1 region, there are two commonly used consensus primer systems designated CP5+/G6+ and MY09/MY11. Both detect a wide variety of human papillomaviruses (HPVs). In this investigation, the authors compared the sensitivity of these approaches with the modification of hot-start PCR on 148 neutral-buffered formaldehyde-fixed cervical biopsies classified as cervical intraepithelial neoplasia (CIN) I to III. The authors chose hot-start PCR because in a previous study it proved more sensitive than cold-start PCR. Furthermore, the authors combined GP5+/GP6+ and MY09/MY11 in a two-step amplification (nested PCR) to analyze further those cases that proved negative with either GP5+/GP6+ or MY09/MY11. The authors found that the two consensus primer systems were equally sensitive with a correlation of 98%. By using GP5+/GP6+, the authors achieved an HPV positivity rate of 95% and with MY09/MY11 94%. Nested PCR did not improve HPV positivity in the CINs included in this study.

Adolescent↗

PubMed1996

Survival in small intestinal adenocarcinoma.

All cases of adenocarcinoma in the duodenum (n = 263) and jejunum/ileum (n = 663), diagnosed between 1960 and 1988, were recruited from the Swedish Cancer Registry. Corrected and overall survival were investigated by sex, age and year of diagnosis with life-table and Cox proportional hazards analyses. The corrected 5- and 10-year survival rates were 39% and 37% for duodenal tumours and 46% and 41% for those in jejunum/ileum (P = 0.16 for difference between sites). The corrected 5- and 10-year survival rates were 52% and 48% for women and 40% and 34% for men with tumours in jejunum/ileum (P = 0.0095 for difference by sex) while no such relation was found in duodenal tumours (P = 0.84). Survival correlated with age at diagnosis for duodenal tumours (P = 0.03377). A Cox proportional hazards analysis revealed a temporal trend with more favourable prognosis in recent years. This study confirms that prognosis of small bowel adenocarcinoma is serious, but gives a more optimistic outlook than many hitherto published series.

Adenocarcinoma↗

PubMed1996

Tumour-induced hypoglycaemia in a patient with insulin-dependent diabetes mellitus.

We report on a case of malignant insulinoma occurring in a patient with genuine insulin-dependent diabetes mellitus (IDDM). A review of cases concerning patients with diabetes mellitus and insulinomas is presented, and reveals only patients with non-insulin-dependent diabetes mellitus (NIDDM). Our case appears to be the first in showing the combination of IDDM and a functioning malignant insulinoma.

Adult↗

PubMed1996

Nonradioisotopic detection and typing of human papillomaviruses by use of polymerase chain reaction and single-strand conformation polymorphism.

The polymerase chain reaction (PCR), used to detect human papillomavirus (HPV), is finding increasing applications in clinical laboratories. The standard method of analysis to detect amplified PCR products is ethidium bromide gel electrophoresis combined with labor intensive blot hybridization. In this study, we describe single-strand conformation polymorphism (SSCP) to detect and genotype simultaneously general primer GP5+/GP6+ amplified HPV DNA using semiautomated electrophoresis on polyacrylamide gels (PAGE) combined with sensitive silver staining. To establish a standard for the band patterns of the various HPV types, we used HPV plasmid DNA, which allowed us to distinguish HPV 6, 11, 16, 18, 31, 33, 35, 45, 51, 52, 56, and 58, covering the most frequently recognized types. All the types tested are separated from each other, demonstrating diverse band patterns, HPV 16 being the most distinct. We also investigated PCR-SSCP for HPV detection and typing of 86 cervical biopsies diagnosed as cervical intraepithelial neoplasia (CIN) I-III and known to be HPV positive by PCR-slot blot hybridization and in situ hybridization. The correlation with SSCP was 91% for in situ hybridization and 98% for PCR-slot blot hybridization. SSCP is reproducible and specific. Its sensitivity is comparable to slot-blot hybridization. The interval to SSCP is approximately 2 h after PCR compared with several days' work when using conventional blot hybridization. We concluded that SSCP may be more advantageous than other PCR-based typing technologies.

Adolescent↗

PubMed1996

Cytological evaluation and molecular human papillomavirus test of cervical scrapings from women treated for condyloma.

The incidence of cervical carcinoma has decreased by about half since cytological screening was introduced in Sweden in the 1960s. This is an encouraging but not altogether satisfactory development. Human papillomaviruses (HPVs) are known to be potential agents in the etiology of cervical cancer. Therefore, an additional HPV test might well improve the detection rate of high-grade cervical intraepithelial neoplasia (CIN). The purpose of this investigation was to compare the correlation of cytology and HPV testing in a pilot study of 94 women recruited from a clinic for sexually transmitted diseases after condyloma treatment and to check earlier established molecular biological assays. Cervical scrapings, taken for simultaneous Pap smear and molecular HPV DNA testing, were assessed by the polymerase chain reaction. Of the 94 women tested, 47 (50%) had normal cytology and negative HPV DNA; 36 (38%) had normal cytology but positive HPV DNA, 26 (72%) of whom harbored high-risk HPVs; 1 (1%) had abnormal cytology but negative HPV DNA, and 10 (11%) had abnormal cytology and positive HPV DNA, 5 (50%) of whom harbored high-risk HPVs. It is concluded that an HPV test would add greater specificity and possibly also greater sensitivity to cytology for detecting or predicting high-grade CIN. This information may be of value when designing future gynecological screening programs.

Adult↗

PubMed1996

Expression of islet amyloid polypeptide in fetal and adult porcine and human pancreatic islet cells.

Aged↗

PubMed1996

Analysis of loss of heterozygosity in microdissected tumor cells from cervical carcinoma using fluorescent dUTP labeling of PCR products.

The use of fluorescently labeled nucleotides (F-dUTP) in the PCR for genetic typing of microsatellite polymorphisms was investigated. Microdissected tumor cells from cervical squamous cancer biopsies were compared with cells from surrounding normal tissue for loss of heterozygosity (LOH) at the mismatch repair gene hMLH1. Removal of unincorporated F-dUTP before analysis is necessary to reduce background fluorescence; ethanol-precipitation was found to be as efficient as the use of a spin column for this purpose. The gel resolution was sufficient to distinguish alleles differing by about four nucleotides. Alleles differing by only one dinucleotide repeat were possible to identify, but the ratio of alleles was difficult to assert with any reliability due to the wide peaks obtained. Single primer-pair and nested amplification systems were shown in reconstitution experiments to reliably quantitate the ratio of alleles. Of 36 cervical cancer biopsies, amplification and typing of the hMLH1 microsatellite marker was successful in 20 cases. Among 9 informative (heterozygous) biopsies, 2 (22%) were found to show LOH.

Alleles↗

PubMed1995

Low efficiency of cytologic screening for cancer in situ of the cervix in older women.

Cytologic screening for cervical cancer has proven to be beneficial in many countries, although the value of this intervention in women older than 50 years remains controversial. The purpose of this study was to investigate the efficiency of detecting cancer in situ by means of a cytologic smear at different ages, with special emphasis on the benefit of screening in women above the age of 50. We analyzed 466,275 smears taken in an open cohort of 118,890 women in Sweden between 1969 and 1988. The number of cancers in situ detected per 1,000 smears, the detection ratio, was used as an outcome measure in univariate analyses and in multivariate regression models. Cancer in situ was detected in 1,076 women in the study cohort. The detection ratio peaked at ages 30 to 34 and decreased heavily during the next 15 years of age. The efficiency of taking smears at ages above 50 was only 20 per cent (OR, 0.19; 95% CI, 0.14-0.26) of that at ages 30 to 34. These results were not changed when adjusting for time period and time interval since the previous smear. In spite of a high incidence of invasive cervical cancer in older women, the benefit of cytologic screening to detect cancer in situ above the age of 50 is uncertain.

Adult↗

PubMed1995

Human biodistribution of [111In]diethylenetriaminepentaacetic acid-(DTPA)-D-[Phe1]-octreotide and peroperative detection of endocrine tumors.

Requisites for preoperative and intraoperative tumor localization with [111In]diethylenetriaminepentaacetic acid-D-[Phe1]-octreotide scanning were explored in 23 patients with endocrine tumors (15 carcinoids, 4 insulinomas, and single cases of gastrinoma, medullary thyroid carcinoma, aldosteronoma, and paraganglioma). The patients were subjected to Octreoscan single photon emission computed tomographic examination prior to surgery and well counter investigation of nuclide uptake in tumors and normal tissues sampled at surgery. Somatostatin receptor-positive tumors demonstrated efficient nuclide accumulation with mean tumor:blood radioactivity ratios of 180-370 (for carcinoids and insulinoma), compared with tissue:blood ratios of 302 for spleen, 42 for liver, and < 10-15 in other normal tissues (pancreas, small intestine, and mesenteric fat). Inefficient preoperative visualization of lesions was related to inconspicuous size, as for primary intestinal carcinoids, tiny liver metastases, and a single small insulinoma. High background activity, pronounced tumor fibrosis, and meager accumulation of tracer also interfered with visualization. Tumor deposits in organs with low background activity (such as carcinoid mesenteric metastases and endocrine pancreatic tumors) were generally most readily detected. Intraoperative investigations with hand-held gamma detector probes were disturbed by obvious high background activity. These investigations revealed two preoperatively unrecognized primary intestinal carcinoids, which, however, were both palpable during surgery. These studies, therefore, had little impact on the surgical strategy.

Adult↗

PubMed1995

Islet amyloid polypeptide (IAPP) in patients with neuroendocrine tumours.

Although IAPP was first discovered and isolated from amyloid deposits in an endocrine pancreatic tumour (EPT), surprisingly few reports have investigated the potential use of IAPP as a marker for neuroendocrine tumour growth. In this study we present results from plasma measurements of IAPP in 102 patients with neuroendocrine tumours. Four of 35 patients (11%) with midgut carcinoid tumours, but none of the patients (4 and 5, respectively) with lung carcinoids or with rectal carcinoids displayed elevated plasma levels of IAPP. Five of 31 patients (16%) with sporadic EPT and 3 of 27 patients (11%) with EPT and multiple endocrine neoplasia type 1 syndrome disclosed elevated IAPP levels. Within the different syndromes, 1/11 individuals with insulinoma, 2/16 with gastrinoma, 0/2 with glucagonoma, 0/3 with VIPoma and 5/26 with non-functioning tumours showed elevated plasma levels of IAPP. In two patients, the plasma IAPP levels were extremely elevated. These patients also exhibited altered glucose homeostasis. In response to a standardised mixed meal test, IAPP increased in parallel to the insulin, pancreatic polypeptide, gastrin and glucose responses. In MEN1 patients with hypercalcaemia due to increased secretion of parathyroid hormone, the plasma levels of IAPP were significantly higher before than after surgical removal of the parathyroid adenomas. However in normocalcaemic patients, no correlation between the blood calcium and plasma IAPP levels was found. Immunocytochemical staining of tumour tissue showed that 9/13 (69%) of insulin producing tumours, 4/14 (29%) of non-functioning tumours and 1/9 (11%) of gastrin producing tumours were IAPP immunoreactive. Amyloid deposits were always IAPP immunoreactive. In conclusion, increased circulating levels of IAPP occurred in 12% of 102 patients with neuroendocrine tumours. In 2 patients with extremely elevated plasma levels of IAPP, effects on glucose homeostasis were recorded. Thus, IAPP may be useful as an additional marker for neuroendocrine tumour growth in selected cases.

Adult↗

PubMed1995

Prognostic value of bcl-2 immunoreactivity in medullary thyroid carcinoma.

Bcl-2 expression has been evaluated immunocytochemically in a series of 33 medullary thyroid carcinomas (MTC) with long-term (mean, 10.3 years) follow-up. Twenty-six of 33 cases showed intense bcl-2 immunoreactivity in more than 25% neoplastic cells. Bcl-2 immunoreactivity did not correlate with several clinicopathologic parameters including sex and age of the patients, sporadic or familial disease, tumor size and stage, amount of amyloid stroma, and immunoreactivity for calcitonin, chromogranin A, proliferating cell nuclear antigen (PCNA), N-myc, and p53. Lack of bcl-2 immunoreactivity, however, correlated significantly (P = .0001) with a shorter survival. Indeed, the seven patients with tumors devoid of bcl-2 immunoreactivity all died of disease within 8 years from the diagnosis. In multivariate analysis, lack of bcl-2 immunoreactivity was an independent predictor of worse prognosis (P = .001 for disease-free survival and P = .0001 for overall survival). None of the other clinicopathologic variable investigated proved to be an independent prognostic parameter. It is concluded that down-regulation of bcl-2 expression in MTC may identify a subset of tumors with a more aggressive clinical course.

Adolescent↗

PubMed1995

Efficiency of organised and opportunistic cytological screening for cancer in situ of the cervix.

Cervical cancer incidence and mortality can be reduced by removal of precursor lesions detected at cytological screening. Organised screening, i.e. regular invitation of defined target groups, is generally considered more effective than opportunistic screening. The latter method however, is predominant in most settings. There is no scientific basis for advocating one type of screening or the other. Our aim was to compare the two types and to analyse their efficiency. We analysed 466,275 smears taken in an open cohort of 118,890 women during 1969-88. A computerised database permitted standardised classification of all smears and complete ascertainment of cancer in situ through record linkage. The number of in situ cancers detected per 1000 smears, the detection ratio, was used as an outcome measure both in univariate analyses and in multivariate logistic regression models. Cancer in situ was detected in 1076 women in the study cohort, with a detection ratio of 3.0 at organised and 2.1 at opportunistic screening, yielding an unadjusted odds ratio of 0.69 (95% CI 0.61-0.79). After adjustment for age and time period, the probability of detecting cancer in situ was around 25% higher with opportunistic than with organised screening (OR = 1.26; 95% CI 1.09-1.46). This difference in favour of opportunistic screening was most pronounced in the first 10 year period and disappeared during the last decade. The difference in efficiency between organised and opportunistic screening in the detection of cancer in situ was slight, if any. The dogma that organised screening is significantly more efficient than the opportunistic type needs reconsideration.

Adult↗

PubMed1995

Expression and prognostic significance of Bcl-2 in ovarian tumours.

The expression of bcl-2 was studied in normal ovaries and in ovarian tumours by immunohistochemical analysis. Normal epithelium was strongly stained in all nine examined ovaries. In comparison, all tumour groups showed a substantially decreased tumour cell expression of the same order of magnitude. Thus, benign tumour cells were weakly stained in two and unstained in two samples, while the remaining eight showed strong expression. Of ten borderline samples, one was unstained and five had weakly and four strongly bcl-2 positive tumour cells. Finally, 24 of 50 malignant tumours showed strong staining, while weak or no expression in tumour cells was found in 16 and 10 samples respectively. The reduced staining deviated significantly from normal ovary for both borderline (P = 0.02) and malignant groups (P = 0.01). Tumour cell staining with the bcl-2 antibody was significantly reduced when tumour mass had to be left behind compared with those with no visible remaining tumour (P = 0.03 and 0.003 for weakly and strongly stained tumours respectively). The expression of bcl-2 in malignant tumour cells was inversely correlated with the expression of p53. Bcl-2 expression was correlated with survival with significantly reduced survival in weakly (P = 0.02) and unstained (P < 0.001) groups compared with those patients having strongly stained malignant tumour cells. This correlation between the presence of bcl-2 and survival was maintained in the subgroups of patients with advanced disease or with residual tumour bulk and was also the case in patients having p53-positive tumours. Our results indicate an inhibitory role of bcl-2 in development and progression of ovarian tumours.

Biomarkers, Tumor↗

PubMed1995

Operative tumour yield obviates preoperative pancreatic tumour localization in multiple endocrine neoplasia type 1.

The efficiency of pancreatic tumour localization was prospectively evaluated in 12 consecutive patients with multiple endocrine neoplasia type 1 (MEN1), who were subjected to extirpation of 56 islet cell neoplasms of 0.2-4 cm in diameter (mean 0.8 cm) during pancreatic resection and enucleation. Computed tomography, angiography of the coeliac trunc and superior mesenteric artery, and percutaneous ultrasound correctly localized 7-12% of the tumours and 21-37% of the 19 lesions measuring at least one centimetre in diameter. Transhepatic portal vein sampling correctly located tumour sites in the proximal or distal portions of the pancreas in four out of six patients, but demonstrated unsatisfactory specificity. Intra-operative ultrasound and bidigital palpation of the pancreas had overall sensitivities of 86 and 45%, respectively, and eight lesions below 0.3 cm in diameter remained undetected with intraoperative ultrasound. It is concluded that diagnosis of endocrine pancreatic neoplasms is biochemical in MEN1 and that broad screening of tumour markers efficiently reveals pancreatic involvement decades before the development of a clinically overt disease. Intra-operative ultrasound is a requisite for pancreatic endocrine surgery in MEN1, and it obviates the need for conventional pancreatic imaging unless a pre-operative search for metastatic disease and anatomical aberrations is considered important.

Adult↗

PubMed1995

Prostaglandins reduce hydrochloric acid-induced increase in duodenal mucosal permeability by a mechanism not related to stimulation of alkaline secretion.

The aim was to investigate whether prostaglandins affect HCl-induced mucosal permeability and to elucidate the role of mucosal bicarbonate secretion in protection. Proximal duodenum of anaesthetized rats were perfused with hydrochloric acid and the effects on luminal alkalinization, mucosal permeability and morphology examined in the absence and in the presence of prostaglandin E2 and/or indomethacin. Luminal alkalinization was determined by back titration of the perfusate and mucosal permeability assessed by measuring the clearance of 51Cr-labelled ethylenediaminetetraacetat ([51Cr]EDTA) from blood-to-intestinal lumen. Perfusion with 100 mM HCl for 5 min increased mucosal permeability sixfold and caused villus tip damage. Luminal administration of PGE2 at a concentration of 10(-6) M had no effect whereas 10(-4) M increased alkalinization by 100% but neither concentration affected the HCl-induced increase in mucosal permeability. PGE2 (10(-4) M), however, improved the ability of the duodenal mucosa to recover from the HCl-induced increase in mucosal permeability. Indomethacin (5 mg kg-1, i.v.) increased alkalinization, augmented HCl-induced mucosal permeability and aggravated mucosal injury. In animals pre-treated with PGE2 plus indomethacin, the HCl-induced increases in mucosal permeability were lower and injury less pronounced than in animals treated with indomethacin alone. No correlation was found between the rate of alkalinization and the HCl-induced increase in mucosal permeability. It is concluded that endogenous prostaglandins reduced the extent of 100 mM HCl-induced duodenal mucosal damage by a mechanism other than the stimulation of alkaline secretion.

Animals↗