[Reply 2: nonchalant and fabricated criticism].
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Antihypertensive Agents↗
Biomedical subjects
G Lindberg
Publications and source records attributed to G Lindberg.
[A comment on calcium antagonists: what has been elucidated?].
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Antihypertensive Agents↗
The role of fine-needle aspiration biopsy in the primary diagnosis of mesenchymal lesions: a community hospital-based experience.
BACKGROUND: The objective of this study was to determine the utility of fine-needle aspiration biopsy (FNAB) in the primary diagnosis of mesenchymal lesions. A total of 162 cases with a diagnosis of benign or malignant mesenchymal lesion (excluding lipoma) on FNAB were retrieved from the cytopathology archives for the years 1990-1997. METHODS: Patients selected for inclusion in this study underwent FNAB as the primary diagnostic modality without a previous tissue diagnosis and had a subsequent surgical procedure for definitive histologic correlation. Seventy-two patients were selected on the basis of the above criteria. RESULTS: Cytologic diagnoses were categorized as benign, malignant, or suspicious for malignancy. Among the 72 cases selected, 42 (58%) benign, 18 (25%) malignant, and 12 (16%) suspicious diagnoses were rendered. Of the patients with benign FNAB diagnoses, 39 of 42 (93%) had a benign lesion on histologic follow-up, and 3 of 42 (7%) had a malignancy. Of the patients with malignant FNAB diagnoses, 17 of 18 (94%) had a malignant lesion and 1 of 17 (6%) proved to be benign. In the subset of suspicious lesions, subsequent histology was benign in 5 of 12 (42%) and malignant in 7 of 12 (58%). CONCLUSIONS: Based on our study, FNAB has excellent accuracy (88%), sensitivity (89%), and specificity (87%) for classifying a mesenchymal tumor as benign or malignant. FNAB can be a rapid and effective tool for the primary categorization of mesenchymal lesions and provide reliable information to the clinician for triage of patients.
Biopsy, Needle↗
Increased mortality in Type II diabetic patients using sulphonylurea and metformin in combination: a population-based observational study.
AIMS/HYPOTHESIS: This study analysed cause-specific mortality in Type II (non-insulin-dependent) diabetic patients using either sulphonylurea alone or in combination with metformin. METHODS: Patients were followed from the first day they were taking either the combination or sulphonylurea alone. Odds ratios by Cox regression analyses were adjusted for age, sex, duration of diabetes, study area, year of inclusion and fasting blood glucose at inclusion. RESULTS: We included 169 patients taking sulphonylurea and metformin in combination and 741 patients taking only sulphonylurea. Mean (range) follow-up time was 6.1 (0.1-13.0) years. The adjusted odds ratio for overall mortality was 1.63 (95% confidence interval 1.27-2.09) in patients taking sulphonylurea and metformin combination vs those using sulphonylurea alone. For mortality from ischaemic heart disease and stroke the adjusted odds ratios were 1.73 (95% confidence interval 1.17-2.55) and 2.33 (95% confidence interval 1.17-4.63), respectively. CONCLUSION/INTERPRETATION: There was a higher cardiovascular mortality in Type II diabetic patients taking sulphonylurea and metformin in combination than in those taking only sulphonylurea. Hence, it cannot be excluded that this kind of combination therapy possibly increases cardiovascular mortality. It is feasible that the increased mortality was secondary to a more aggressive type of diabetes in the patients using sulphonylurea and metformin in combination. Combination therapy is known to promote additional blood glucose reduction but there is as yet no evidence that a sulphonylurea and metformin combination is more beneficial on micro- or macrovascular disease than sulphonylurea or metformin alone.
Blood Glucose↗
Loss of Dpc4 expression in colonic adenocarcinomas correlates with the presence of metastatic disease.
DPC4 is a candidate tumor suppressor gene on chromosome 18q21, a region that shows high frequencies of allelic losses in pancreatic and colorectal adenocarcinomas. Biallelic inactivation of DPC4 has been reported in half of pancreatic cancers, but are relatively infrequent in other tumor types. The role of DPC4 inactivation in colorectal neoplasms has not been fully characterized. An immunohistochemical assay for Dpc4 protein expression has been recently developed and shown to be a sensitive and specific surrogate for alterations in the DPC4 gene. In this study we examined the expression of Dpc4 protein in formalin-fixed archival tissue from 83 colorectal lesions, including 19 adenomas and 64 sporadic adenocarcinomas (11 stage I, 13 stage II, 17 stage III, and 23 stage IV cancers). None of the adenomas or stage I adenocarcinomas showed loss of Dpc4 expression, whereas one of 13 (8%) stage II, one of 17 (6%) stage III, and five of 23 (22%) of stage IV cancers showed loss of Dpc4 expression. There was a borderline significant difference in loss of Dpc4 reactivity in colorectal tumors with distant metastasis at presentation (22%) versus primary tumors without distant metastasis (5%) (Fisher's exact test, P = 0.05; chi(2) = 0.04). Poorly differentiated histology or status of pericolonic lymph nodes did not affect Dpc4 expression. Alterations in DPC4 are involved in the progression of a subset of colorectal carcinomas, especially those that present with advanced disease. In the sequential pathogenesis of colorectal tumors, inactivation of DPC4 is likely to be a late event.
Adenocarcinoma↗
Curing Helicobacter pylori infection in patients with duodenal ulcer does not provoke gastroesophageal reflux disease.
BACKGROUND: It has been suggested that the incidence of gastroesophageal reflux disease (GERD) increases after successful eradication of Helicobacter pylori infection. We present data on development of GERD from a controlled study of H. pylori eradication in 165 duodenal ulcer patients. METHODS: Patients (mean age, 55 years; 102 men; current smokers; n = 74) were randomly assigned 2: 1 to receive omeprazole, 40 mg twice daily, in combination with either amoxicillin, 750 mg twice daily, or placebo. Endoscopy and dyspeptic symptoms, including heartburn, were assessed at inclusion and at 6, 12, and 24 months after treatment. In addition, symptoms were assessed at 18 months. Patients with erosive esophagitis or reflux symptoms requiring treatment at inclusion were not included in the study. RESULTS: Fifty-one of 145 (35%) evaluable patients developed heartburn, and 13 of 145 (9%) developed esophagitis during follow-up. The life-table analysis of the cumulated risk of developing heartburn showed that patients whose H. pylori infection was eradicated had a significantly lower risk for developing heartburn than those with persistent H. pylori infection. The groups did not show any difference in cumulative risk of developing esophagitis. CONCLUSION: Our data show that successful eradication of H. pylori infection does not increase the incidence of GERD in duodenal ulcer patients.
Adult↗
Ectopic production and localization of beta-human chorionic gonadotropin in lymphoepithelioma-like carcinoma of the cervix: a case report.
A 32-year-old woman underwent a suction curettage for missed abortion. The initial serum human chorionic gonadotropin (beta-hCG) level was 40 IU/ml. The histologic examination of the uterine curettage specimen showed scant strips of a poorly differentiated malignant neoplasm and no chorionic villi. The tumor showed strong immunoreactivity for cytokeratin (AE1/AE3) and beta-hCG but no reactivity for human placental lactogen. The combination of histologic appearance, beta-hCG immunoreactivity, and elevation of serum beta-hCG raised a strong suspicion for epithelioid trophoblastic tumor (ETT). Postcurettage serial serum beta-hCG levels remained in the range of 20 to 45 micrograms/ml. Computerized tomographic scan showed a 1.0-cm circumscribed mass in the upper endocervix. A radical hysterectomy and pelvic lymphadenectomy were performed. Gross examination of the hysterectomy specimen likewise showed a well-circumscribed mass in the upper endocervix. Histologic examination revealed an undifferentiated carcinoma accompanied by intense lymphoplasmacytic infiltrate. A final diagnosis of lymphoepithelioma-like carcinoma (LELC) was rendered. LELC with elevated serum beta-hCG level and immunoreactivity to beta-hCG should be distinguished from ETT in a small endocervical curettage sample.
Abortion, Missed↗
Markers of inflammation and prediction of diabetes mellitus in adults (Atherosclerosis Risk in Communities study): a cohort study.
BACKGROUND: Type 2 diabetes mellitus and atherosclerotic cardiovascular disease have common antecedents. Since markers of inflammation predict coronary heart disease and are raised in patients with type 2 diabetes, we investigated whether they predict whether people will develop type 2 diabetes. METHODS: 12,330 men and women, aged 45-64 years, were followed up for a mean of 7 years. We analysed the association between different markers of acute inflammation and subsequent diagnosis of diabetes. In a subgroup of 610 individuals selected originally for an unrelated atherosclerosis case-control study, we also investigated diabetes associations with total sialic acid and orosomucoid, haptoglobin, and alpha1-antitrypsin. FINDINGS: 1335 individuals had a new diagnosis of diabetes. Adjusted odds ratios for developing diabetes for quartile extremes were 1.9 (95% CI 1.6-2.3) for raised white-cell count, 1.3 (1.0-1.5) for low serum albumin, and 1.2 (1.0-1.5) for raised fibrinogen. In the subgroup analysis, individuals with concentrations of orosomucoid and sialic acid of more than the median had odds ratios of 7.9 (2.6-23.7) and 3.7 (1.4-9.8), respectively. Adjustment for body-mass index and waist-to-hip ratio lessened the associations; those for white-cell count (1.5 [1.3-1.8]), orosomucoid (7.1 [2.1-23.7]), and sialic acid (2.8 [1.0-8.1]) remained significant. INTERPRETATION: Markers of inflammation are associated with the development of diabetes in middle-aged adults. Although autoimmunity may partly explain these associations, they probably reflect the pathogenesis of type 2 diabetes.
Autoimmunity↗
Octreotide for nausea and vomiting after chemotherapy and stem-cell transplantation.
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Adult↗
Molecular abnormalities associated with endocrine tumors of the uterine cervix.
Objective. We studied the molecular abnormalities involved in the pathogenesis of endocrine tumors of the uterine cervix. Methods. We obtained DNA from precisely microdissected archival tissue from 15 endocrine tumors of the uterine cervix, consisting of 5 carcinoids (1 typical, 4 atypical), 2 large cell neuroendocrine carcinomas, and 8 small cell carcinomas. We investigated the presence of high-risk (types 16 and 18) and intermediate-risk (types 31 and 33) human papilloma virus (HPV) sequences, TP53 and K-ras gene mutations, and loss of heterozygosity (LOH) at 9 genes/chromosomal regions, including 3p14.2/FHIT, 3p14-p21, 3p21, 3p22-p24, 5q21-q22/APC-MCC region, 9p21/CDKN2, 11q23/MEN1, 13q/RB, and 17p/TP53. Results. HPV sequences were detected in 8 (53%) tumors, HPV 16 in 2 cases, and HPV 18 in 2 cases. LOH at 9p21 (43%) and localized 3p deletions (47%) were the most frequent allelic losses found. Allelic losses at 5q21-q22/APC-MCC region, 11q23/MEN1, and 13q/RB were infrequent. TP53 gene mutations were detected in 7 (47%) tumors (1 atypical carcinoid and 6 carcinomas). HPV sequences were demonstrated in 4 of the 7 cases with TP53 gene mutations. No K-ras mutations were detected. Conclusion. The molecular changes present in endocrine tumors of the uterine cervix have distinct features. They incorporate those present in the neuroendocrine tumors of the lung (high frequency of TP53 gene abnormalities and 9p21 deletions) with those detected in squamous cell carcinomas of the cervix (high-risk HPV sequences and localized 3p deletions).
Carcinoid Tumor↗
Clinical value of symptom assessment in patients with constipation.
PURPOSE: This study was designed to evaluate symptoms and clinical findings in a prospective series of patients with chronic constipation. METHODS: A total of 155 consecutive patients with intractable constipation underwent detailed symptom registration, anorectal manometry, electromyography, colonic transit time measurement, and defecography. RESULTS: All investigations were completed by 134 patients (112 females) with a median age of 52 (range, 17-79) years. Whole-gut transit time was delayed in 55 patients (41 percent), pelvic floor dysfunction was diagnosed in 59 patients (44 percent), but in 35 percent of patients both transit time and pelvic floor function were found to be normal. Three symptoms were shown to have an independent value for the diagnosis of slow-transit constipation. Patients with slow transit more often reported two or fewer stools per week (84 vs. 46 percent), laxative dependence (87 vs. 44 percent), and a history of constipation since childhood (58 vs. 22 percent) than did those with normal transit. Pelvic floor dysfunction was associated with a higher prevalence of backache (53 vs. 33 percent) and a lower prevalence of normal stool frequency (19 vs. 36 percent), heartburn (12 vs. 27 percent), and a history of anorectal surgery (7 vs. 21 percent) compared with those with normal pelvic floor function. All four symptoms retained an independent value in the logistic regression analysis for pelvic floor dysfunction. Two symptoms characterized the group with normal transit and normal pelvic floor function: normal stool frequency and alternating diarrhea and constipation. CONCLUSIONS: Symptoms are good predictors of transit time but poorer predictors of pelvic floor function in patients with constipation.
Adolescent↗
Utilization of cardiovascular drugs (blood pressure lowering drugs, lipid lowering drugs and nitrates) and mortality from ischaemic heart disease and stroke. An ecological analysis based on Sweden's municipalities.
OBJECTIVE: To perform an ecological study in an effort to generate questions concerning the preventive impact of various cardiovascular drugs on mortality from stroke and ischaemic heart disease (IHD) in the community, and to explore the association between sales of nitrates and mortality from stroke and IHD. METHODS: Out-patient drug utilization (sales) of blood pressure lowering drugs, lipid lowering drugs and nitrates were categorized in four groups of equal size by quartiles and compared with mortality from IHD and stroke, using the group of municipalities with the lowest utilization as reference, from 1989 to 1993 in 283 of Sweden's 288 municipalities, by Poisson regression. Adjustments were made for population size, age and gender proportions, the utilization rate of cardiovascular drugs other than the tested drug group and location of the municipality. RESULTS: Compared with the group of municipalities with the lowest sales and adjusting only for population size, mortality from IHD and stroke increased with the extent of utilization of blood pressure lowering drugs and nitrates. In contrast, mortality decreased with increased utilization of lipid lowering drugs. After further adjustments by percentage of men, age structure, geographical location (mid-points) of the municipalities, and, as a proxy for cardiovascular disease, the sales of cardiovascular drugs other than the tested drug group, the increased risk associated with blood pressure lowering drugs disappeared, and there was a dose-response association between sales of diuretics and old antihypertensives and decreasing mortality, sales of nitrates continued to be associated with an increased risk, and the low mortality risk associated with sales of lipid lowering drugs persisted. CONCLUSION: Lipid lowering drugs may have a preventive impact in the general population, but the preventive impact of blood pressure lowering drugs, with the exception of diuretics and old antihypertensives, may be low in many municipalities. The safety of nitrates needs more investigation at the individual level.
Antihypertensive Agents↗
Tumor necrosis factor inhibitor ameliorates murine intestinal graft-versus-host disease.
BACKGROUND & AIMS: Transfer of T helper cells from DBA/2 mice to irradiated allogeneic B6D2F1 mice leads to development of colonic graft-versus-host disease with pathological features of inflammatory bowel disease. To examine the role of tumor necrosis factor (TNF) in graft-versus-host disease enteropathy, an adenoviral vector encoding a TNF inhibitor protein was administered. METHODS: Irradiated B6D2F1 mice were infused with DBA/2 bone marrow and spleen cells. Mice then received either a control beta-galactosidase-encoding adenovirus or an adenovirus encoding a TNF inhibitor, composed of the extracellular domain of the human 55-kilodalton TNF receptor linked to the murine immunoglobulin G1 heavy chain. Mucosal permeability to sucralose and colonic histology were assessed 14 and 25 days after transplantation. RESULTS: Less diarrhea was observed in DBA/2 --> B6D2F1 mice expressing the TNF inhibitor, and colonic sections from these mice had significantly less inflammation and epithelial cell abnormalities. In TNF inhibitor recipients, mucosal permeability to sucralose was similar to that in nonirradiated control mice and significantly less than in recipients of the control adenovirus. CONCLUSIONS: TNF inhibition decreases the severity of enteropathy in the DBA/2 --> B6D2F1 murine model of colonic graft-versus-host disease.
Animals↗
Serum sialic acid and sialoglycoproteins in asymptomatic carotid artery atherosclerosis. ARIC Investigators. Atherosclerosis Risk in Communities.
Serum total sialic acid (S-TSA) is a recently identified risk marker for atherosclerosis and cardiovascular mortality. The purpose of this study was to evaluate the influence of three sialic acid rich glycoproteins (orosomucoid, haptoglobin, and alpha1-antitrypsin) on the relationship between S-TSA and carotid atherosclerosis. The mean S-TSA was 0.045 g/l higher among cases than controls (P<0.001) in 310 45-64 year-old male and female pairs of carotid atherosclerosis cases and disease-free controls from the Atherosclerosis Risk in Communities (ARIC) Study. Also mean serum levels of the glycoproteins were significantly higher in cases compared to controls. In a conditional multiple logistic regression model with the glycoproteins as independent variables, orosomucoid was correlated most strongly with case control status. However, when incorporated into the mathematical model, S-TSA not only contributed additional information as to the risk of atherosclerosis; none of the three glycoproteins contributed further once S-TSA had been accounted for. Thus, some other source of serum sialic acid or variations in the degree of sialylation of glycoproteins may be essential for understanding the relation between S-TSA and atherosclerosis.
Aged↗
Signet-ring cell variant of small lymphocytic lymphoma with a prominent sinusoidal pattern.
Signet-ring cell lymphoma is a rare morphologic variant of non-Hodgkin's lymphoma characterized by neoplastic lymphoid cells with cytoplasmic vacuoles or eosinophilic globules that impart a signet-ring cell morphology. Although most cases are variants of follicular center B-cell lymphomas, this pattern also can be seen in T-cell lymphomas. An indolent clinical course and prolonged survival have characterized the majority of published cases. We document the case of a 62-year-old African-American woman with diffuse small lymphocytic signet-ring lymphoma having a predominant sinusoidal growth pattern, which, to our knowledge, has not been previously reported. The prominent sinusoidal pattern of signet-ring lymphocytes contributes to its confusion with metastatic signet-ring cell adenocarcinoma. The correct diagnosis is greatly facilitated by the use of appropriate immunohistochemical stains for lymphoid markers.
Axilla↗
Dopamine reduces gastric tone in a dose-related manner.
BACKGROUND: Dopamine may have effects on gastrointestinal motility. The aim of this study was, therefore, to determine whether dopamine reduces gastric tone and whether the effects of dopamine can be blocked by a dopamine antagonist. METHODS: Eight healthy male volunteers were studied on two occasions in a randomized order. A continuous infusion of incremental doses of dopamine (2.5, 5.0, 7.5 microg kg(-1) min(-1)) was given on both occasions. Ten milligrams of the dopamine-antagonist metoclopramid was given before the dopamine infusion on one occasion and during the dopamine infusion (7.5 microg kg(-1) min(-1)) on the other occasion. The gastric tone was measured by an electronic barostat, an instrument with an electronic control system that maintains a constant preset pressure within an air-filled, flaccid intragastric bag by means of momentary changes in the intragastric volume of air. Volume and pressure in the gastric bag were continuously recorded by the electronic barostat and sampled in a computer. RESULTS: Dopamine induced a dose-related increase in the intragastric bag volume. Metoclopramid given as a 10 mg i.v. bolus dose during the infusion of dopamine significantly decreased the intragastric bag volume, but 10 mg of metoclopramid i.v. before the dopamine infusion did not influence the bag volume per se. CONCLUSION: Dopamine decreases gastric tone in a dose-related manner and 10 mg of the dopamine-antagonist metoclopramid is not enough to fully reverse these effects.
Adult↗
Endoscopic removal of an esophageal fibrovascular polyp.
Fibrovascular polyps are intraluminal pedunculated esophageal polyps, which can produce devastating consequences if untreated. Therapy for these lesions is traditionally surgical, with esophagotomy. The present report describes a case of endoscopic removal of a fibrovascular polyp, alleviating the need for hospitalization or further interventions. The natural history, clinical presentation, diagnostic evaluation, and therapies are reviewed.
Electrocoagulation↗
Gastroesophageal reflux in healthy subjects. Significance of endoscopic findings, histology, age, and sex.
BACKGROUND: Our aim was to evaluate which specific factors are of importance for the gastroesophageal reflux seen in presumably healthy subjects. METHODS: We investigated 57 healthy, asymptomatic volunteers with computer-aided medical history interrogation, endoscopy, biopsy specimens from the distal esophagus, manometry, and 24-h ambulatory pH-monitoring. RESULTS: Eight subjects (14%) claimed intermittent reflux symptoms at the computer interview, but they did not have more acid reflux at pH-monitoring than asymptomatic volunteers. Thirteen subjects (23%) had abnormalities at endoscopy, 3 of whom had an erosion in the distal esophagus, and 12 had hiatus hernia. Subjects with hiatus hernia had increased acid reflux at 24-h pH-monitoring compared with those without hernia. If subjects with hernia were excluded, the degree of acid reflux was similar in all age groups. Men had more acid reflux than women, and these differences persisted if subjects with hernia were excluded. There was no correlation of histologic signs of esophagitis in the distal esophagus, lower esophageal sphincter pressure, smoking habit, or body mass index with reflux of acid to the esophagus. CONCLUSION: Hiatus hernia is a common finding in healthy subjects, and it predisposes to gastroesophageal acid reflux. Histologic abnormalities are poorly related to acid reflux in healthy volunteers. We found increased acid reflux in healthy men compared with women, but larger studies are needed to confirm these findings. Symptom evaluation is not sufficient to exclude significant gastroesophageal reflux in healthy volunteers, and we suggest that the possibility of esophageal abnormalities should be excluded by endoscopy in comparative studies of gastroesophageal reflux disease.
Adult↗