Ulla Engel

Regional variations in histomorphometric bone dynamics from the skeleton of an osteoporotic woman

SummaryHistomorphometric evaluation of bone formation in an intravital tetracycline-labeled skeleton of a suddenly deceased osteoporotic woman is presented. The 24 skeletal sites investigated displayed substantial regional variations which, for two out of four cortical bone dynamics and all trabecular bone dynamics, were significantly higher than the intraspecimen variation. Poor agreement was found between bone formation in left- and right-sided iliac crest specimens. Furthermore, no agreement was found between trabecular bone formation and amount of hematopoetic marrow. With all the limitations that the study of a single patient involves it is suggested that (1) bone biopsy in individual patients should not be the only basis for therapeutic decisions in postmenopausal osteoporosis; (2) amount of hematopoietic marrow does not seem to influence bone formation; and (3) bone formation in the skeleton display large regional variations, which are larger for the fraction of labeled surfaces than for appositional rate.

Role of endothelium and nitric oxide in histamine‐induced responses in human cranial arteries and detection of mRNA encoding H1‐ and H2‐receptors by RT‐PCR

Histamine induces relaxation of human cranial arteries. Studies have revealed that the relaxant histamine H1‐receptor predominates in human cerebral and the H2‐receptor in temporal arteries, while H1‐ and H2‐receptors are of equal importance in the middle meningeal artery. The purpose of the present study was to examine the role of the endothelium and nitric oxide in histamine‐induced responses and to show the presence of mRNA encoding H1‐ and H2‐receptors in human cranial arteries. Electrophoresis of polymerase chain reaction (PCR) products from human cerebral, middle meningeal and temporal arteries, demonstrated products corresponding to mRNA encoding both H1‐ and H2‐receptors in arteries with and without endothelium. The amplified PCR products were sequenced and showed 100% homology with the published sequences of these histamine receptors. A sensitive in vitro system was used to study vasomotor responses to histamine. In precontracted cerebral, middle meningeal and temporal arteries with and without endothelium, histamine caused a concentration‐dependent relaxation with Imax values between 87% and 81% and pIC50 values between 8.14 and 7.15. In arteries without endothelium the histamine‐induced relaxation was significantly less potent (Imax values between 87% and 66% and pIC50 values between 7.01 and 6.67) than in cranial arteries with an intact endothelium. The addition of histamine to arteries without endothelium and pretreated with the histamine H2‐antagonist, cimetidine (10−5 M), caused a concentration‐dependent contraction of the cranial arteries with Emax values between 86% and 29% and pEC50 values between 7.53 and 6.77. This contraction was blocked by the histamine H1‐receptor antagonist, mepyramine (10−7 M), and even turned into a relaxation with Imax values between 84% and 14% and pIC50 values between 7.42 and 5.86. The nitric oxide synthase inhibitor NG‐nitro‐L‐arginine methyl ester (L‐NAME, 3×10−5 M) significantly inhibited the relaxant response to histamine in cerebral and temporal arteries (pIC50 values between 7.43 and 7.13). The combined treatment with L‐NAME (3×10−5 M) and cimetidine (10−5 M) caused a further displacement of the concentration‐response curve (pIC50 values between 7.14 and 6.57) and decreased the maximum relaxant responses in all three cranial arteries (Imax values between 62% and 39%). In conclusion, this is the first study which show mRNA encoding histamine H1‐ and H2‐receptors in human cranial arteries. The results indicate that histamine‐induced relaxation of human cranial arteries is partially mediated via an endothelial H1‐receptor coupled to the production of nitric oxide and partially via a H2‐receptor associated with the smooth muscle cells. In addition, there is evidence for a contractile H1‐receptor in the smooth muscle cells in these arteries.

Neoplasm to neoplasm metastasis: a renal oncocytoma with metastatic bronchogenic carcinoma

An unusual case of metastasis of neoplasm to a benign neoplasm is reported. The initial malignancy, a small-cell bronchogenic carcinoma, was found to have metastasis to a renal oncocytoma. A review of the literature indicates, according to our knowledge, no similar case.

Peptidergic and non-peptidergic innervation and vasomotor responses of human lenticulostriate and posterior cerebral arteries.

The aim of the present study was to compare in man the innervation pattern and the functional responses to neuronal messengers in medium sized lenticulostriate and branches of the posterior cerebral arteries (PCA). The majority of the nerve fibers found were sympathetic and displayed specific immunoreactivity for tyrosine hydroxylase (TH) and neuropeptide Y (NPY). Only few nerve fibers displayed vasoactive intestinal polypeptide (VIP), calcitonin gene-related peptide (CGRP) and substance P (SP) immunoreactivity. In both arteries, the contractions induced by noradrenaline (NA), NPY and 5-hydroxytryptamine (5-HT) and the relaxant responses induced by acetylcholine (ACh), VIP and pituitary adenylate cyclase activating peptide-27 (PACAP) as well as CGRP and SP were compared in vitro. In conclusion, there was no major difference in innervation pattern or vasomotor sensitivity (pEC50 and pIC50 values) between the two vessels. However, the general pattern indicates stronger vasomotor responses (Emax and Imax) in the PCA branches as compared to the lenticulostriate arteries which may lend support for the clinical observation of a difference in stroke expression between the two vascular areas.

Hypertension and left ventricular hypertrophy in patients with spontaneous subarachnoid hemorrhage.

One hundred and eighteen consecutive cases of spontaneous subarachnoid haemorrhage seen at one hospital during a three-year period were examined to assess the prevalence of hypertension and the correlation between the presence of hypertension and the risk of early death. Eighty-seven of the patients had intracranial aneurysms. The diagnosis of hypertension was determined by means of three complementary criteria: a history of treatment with antihypertensive drugs; systolic and/or diastolic blood pressure levels > or = 160 and 95 mmHg, respectively, measured by the general practitioners of the patients before the onset of the subarachnoid haemorrhage; and the presence of left ventricular hypertrophy determined by echocardiography and/or necropsy. The major findings were as follows: 1) hypertension was present in at least 41% of the patients; 2) in 37% of 51 patients with no history of hypertension before the haemorrhage, left ventricular hypertrophy was diagnosed; and 3) the frequency of hypertension was significantly higher in patients who died within 14 days after the bleeding episode compared with patients surviving this period.

Lectin staining of renal tubules in normal kidney

Lectins are glycoproteins able to bind carbohydrate structures specifically. In this study we applied six different lectins on normal renal tissue to investigate their specificity for different segments of the renal tubular system. The following lectins were used: jacalin, peanut agglutinin (PNA), wheat germ agglutinin (WGA), phytohemagglutinin E (PHA‐E), concanavalin A (Con A), and Dolichos biflorus agglutinin (DBA). Particular attention was paid to jacalin lectin as its staining properties respecting the renal tubular system were not known. We showed that jacalin lectin strongly stains the luminal border of distal tubules, as well as single cells of the collecting tubules. As regards the other five lectins, PNA stained distal tubules, WGA the whole nephron, PHA‐E proximal tubules, and Con A and DBA a few cells of the loop of Henle.

Significance of acquired diverticular disease of the vermiform appendix: a marker of regional neoplasms?

Aim To assess the prevalence of acquired diverticulum of the appendix (DA), including incipient forms and its possible significance as a marker of local/regional neoplasms. Materials and Methods The pathology database at Hvidovre Hospital was searched for appendix specimens, received between 2001 and 2010, coded for DA or for a space-occupying lesion. Slides were reviewed to determine DA status and the nature of lesions possibly causing DA. Result Among 4413 appendix specimens, DA were identified in 39 (0.9%, CI 0.6% to 1.2%) cases, 17 (43.6%, 28.0% to 59.2%) of which additionally harboured an appendiceal neoplasm/neoplastic precursor, whereas this figure was 1.2% (CI 0.9% to 1.6%) for non-DA specimens (p<0.0001). Six of the 39 DA specimens comprised incipient DA, three of which coexisted with appendiceal neoplasms. In addition, local/regional non-neoplastic lesions (six cases) and colorectal carcinomas (four cases) coexisted with DA. Conclusion DA has significance as a putative marker of local/regional neoplasms. Therefore, a DA specimen proved significantly more likely to harbour a neoplastic growth than a non-DA counterpart. Submission for microscopy of the entire DA specimen, whether transmural or only incipient, and a comment in the pathology report on the occasional concurrence of local/regional neoplasms in this setting seem appropriate. The observation of DA may thus provide a valuable contribution in the diagnostic process.

CD3 immunohistochemical staining in diagnosis of lymphocytic colitis

Microscopic colitis (MC) is a common cause of chronic watery diarrhea. Traditionally, MC encompasses the 2 subgroups lymphocytic colitis (LC) and collagenous colitis, but recently, an additional subgroup, MC incomplete, has been introduced. Distinguishing between the subgroups relies exclusively on histopathologic evaluation. In the present study, 4 pathologists evaluated 156 archived biopsies originally diagnosed as LC or LC incomplete (LCi). Each pathologist assigned a diagnosis of LC, LCi, or nonspecific inflammation to all cases at 2 independent assessments. At the first assessment, hematoxylin and eosin (HE) stainings were available. At the second assessment, a supplementary CD3 immunohistochemical staining was also available. The aim was to evaluate whether a supplementary CD3 would increase the diagnostic agreement among pathologists, and whether a CD3 stain would change the diagnosis based on HE staining only. After the complete assessment, the cases were divided into 3 groups, that is, full agreement, partial agreement, and disagreement. The CD3 staining increased the number of cases with full agreement from 60 to 78. One hundred thirty-one cases with agreement or partial diagnostic agreement based on HE + CD3 were compared with the HE diagnoses. In 44 (34%) of 131 cases, CD3 changed the diagnosis. Cases assigned to the LCi category based on HE were often changed by a supplementary CD3. Conclusively, it is recommended to use a CD3 before giving the histopathologic diagnosis of LCi.

Biopsies of colorectal clinical polyps – emergence of diagnostic information on deeper levels

Although the occasional appearance of a normal histology of biopsies from endoscopic colorectal (CR) polyps is generally held knowledge, its prevalence has rarely been focused on, and the yield of additional sections in such cases has been previously addressed in merely four communications. Hitherto, this issue has not been discussed in the context of the clinical setting. The prime aim of this study was to evaluate the yield of step sectioning CR biopsies, considered non-diagnostic (non-diagnostic biopsies (NDB)) on routine sections. The results are correlated with the indications for endoscopy. Additionally, an appropriate, cost-effective approach for handling NDB was sought. Biopsies from 480 clinical polyps were prospectively evaluated by one of three gastrointestinal pathologists and classified as (a) diagnostic biopsies (DB), comprising neoplastic polyps, hyperplastic polyps (HP), sessile-serrated polyp, other diverse causes of polyp formation and (b) NDB comprising normal histology (group 1), suspicious of either adenoma (group 2) or HP (group 3). Material grouped 1-3 was subsequently step-sectioned (three sections prepared from each of nine additional levels). The biopsy specimens were obtained from 245 endoscopies and stratified in the following categories according to the clinical indications: relevant symptoms (symptomatic, n=127), previously documented sporadic large bowel neoplasia (follow-up, n=99), and documented or presumed hereditary condition that confer an increased risk of CRC (hereditary, n=19, including 15 hereditary non-polyposis colorectal cancer (HNPCC) cases). Sixty-five (13.5%) of the 480 samples were classified as NDB (normal morphology n=49, suspicious of adenoma n=5, suspicious of HP n=11), constituting roughly 10% of all biopsies from the symptomatic and the follow-up categories, 32.1% of samples from the hereditary cases, the difference between the hereditary and the non-hereditary cases being statistically significant (p<0.0001). Upon leveling the 65 NDB, a DB emerged in 24 (36.9%) cases, with no significant difference in the yield in relation to the delineated indication categories. Thereby, diagnostic information was obtained with three additional levels in 15 cases, the remaining 9 cases requiring additional sections, ranging from 4 to 8 levels. The present step sectioning approach implied an extra expense of about 112 US

Automated image analysis in the study of collagenous colitis.

for each NDB converted to a DB. The higher prevalence of NDB in relation to genetic disorders probably reflects sampling of particularly diminutive lesions. Given the high yield of step sectioning NDB coupled with an acceptable price, our strategy delineated here is recommended in routine practice with the modification of an initial preparation of sections from merely three levels, and if still non-diagnostic, supplementation with additional five levels.