Biomedical subjects

R Koren

Publications and source records attributed to R Koren.

At least 37 records · Page 2Linked to original sources

PubMed2001

Gastric corpus mucin expression after partial gastrectomy, in relation to colonization with Helicobacter pylori.

Twelve different genes for mucin have been described. MUC5AC and MUC6 encode the secreted apomucins of the stomach. A gradient from the surface epithelium (foveola) to the glands is typical for MUC5AC synthesis, whereas a gradient in the opposite direction was found for MUC6. Our goal was to determine the distribution of MUC5AC and MUC6 in the postoperative stomach, with relation to the H. pylori status. Gastric corpus biopsy specimens from patients who underwent partial gastrectomy were examined by immunohistochemistry for mucin gene (MUC5AC and MUC6) apoproteins. We used polyclonal antibodies for amino acid tandem repeats of both proteins. A scoring system (0-3) was used to assess staining intensity at four sites: the lumen, the foveola, the mucous neck cells, and the glands. Helicobacter pylori status was determined by histology and rapid urease test and was considered positive or negative when both tests were positive or negative, respectively. We studied 19 H. pylori-positive and 32 H. pylori-negative patients. No significant change in MUC5AC or MUC6 synthesis and secretion was demonstrated between H. pylori-positive or -negative patients. A gradient similar to that shown for the intact stomach (from the surface epithelium to the glands) for MUC5AC protein and an increase of MUC6 protein presentation from the mucous neck cell to the glands were demonstrated. The pattern of MUC5AC protein synthesis was not different between H. pylori-positive and -negative patients in the postoperative stomach. MUC6 expression was higher in the foveola in H. pylori-positive patients, whereas there was no difference in the other cell layers.

Gastrectomy↗

PubMed2001

Does Helicobacter pylori affect gastric mucin expression? Relationship between gastric antral mucin expression and H. pylori colonization.

BACKGROUND/OBJECTIVE: Helicobacter pylori colonizes the gastric mucous gel layer, the surface epithelium and glands. It has been shown that H. pylori infection causes aberrant expression of gastric mucins MUC 5 and MUC 6. This study aimed to determine the distribution of MUC 5 and MUC 6 in the gastric antrum of dyspeptic patients, and to investigate changes in this pattern in the presence of H. pylori and after successful eradication. MATERIALS AND METHODS: Gastric antrum biopsy specimens were examined by immunohistochemistry for mucin gene (MUC 5 and MUC 6) expression. Polyclonal antibodies were used to detect amino acid tandem repeats of each protein. A scoring system (0-3) was used to assess staining intensity at three sites: foveola, mucous neck cells and glands. H. pylori status was determined by histology and rapid urease test, and considered positive or negative when both tests were positive or negative, respectively. The study included 49 patients positive for H. pylori, in 36 of whom successful eradication was performed, and 11 H. pylori-negative patients. RESULTS: There was a gradient of MUC 5 expression, higher to lower, from the surface to the glands, which was more pronounced before eradication. Increased MUC 5 synthesis in the mucous neck cells and in the glands was found after H. pylori eradication (P = 0.016). MUC 6 was synthesized in the glands more than in the mucous neck cells or foveola. MUC 6 was also secreted into the lumen and probably comprised the superficial part of the unstirred mucous layer. CONCLUSION: The change in MUC 5 synthesis may reflect H. pylori colonization.

Adult↗

PubMed2001

Relationship between Helicobacter pylori CagA status and colorectal cancer.

OBJECTIVES: Infection with Helicobacter pylori, particularly with strains positive for CagA protein, increases the risk of gastric adenocarcinoma. Few studies have explored the possible association between H. pylori infection and colorectal cancer. This study evaluated whether the seroprevalence of CagA in H. pylori-infected patients affected risk for colorectal cancer independently of H. pylori status. METHODS: In this study, we tested serum IgG antibodies against H. pylori (ELISA) and CagA protein (Western blot assay) in 67 patients with colorectal adenocarcinoma, 36 with gastric adenocarcinoma, 47 with other malignancies (cancer controls), and 45 hospitalized for transesophageal echocardiography (TEE controls). Colonic cancer and gastric cancer patients with H. pylori infection were compared to each control group and to the pooled controls using simple and adjusted analyses. RESULTS: H. pylori infection was noted in 50 colon cancer patients, 31 gastric cancer patients, 31 cancer controls, and 32 TEE controls. In all, 41 (82%), 29 (94%), 11 (35%), and 13 (41%), respectively, of these H. pylori-positive sera expressed CagA reactivity (p < 0.001 for all pairwise comparisons between cases and controls). In the adjusted analysis, infection with H. pylori CagA+ compared to H. pylori CagA- was associated with increased risk for colorectal adenocarcinoma (odds ratio = 10.6; 95% CI = 2.7-41.3; p = 0.001) and gastric adenocarcinoma (odds ratio = 88.1; 95% CI = 6.3-1229.2; p = 0.001). CONCLUSIONS: Among patients infected with H. pylori, CagA+ seropositivity is associated with increased risk for both gastric and colonic cancer. This finding should stimulate additional research into the role of cagA+ H. pylori infection in the development of colorectal cancer.

Antibodies, Bacterial↗

PubMed2001

Reduced expression of activin A in focal lymphoid agglomerates within nasal polyps.

It has been previously reported that activin A, a homodimer of the betaA inhibin subunit, is secreted by stromal cells from mouse bone marrow and causes apoptotic death of mouse plasmacytoma tumor cells. Recent in vitro studies have also implicated this cytokine in the suppression of normal B-cell lymphopoiesis. In this study we examined the occurrence of activin A in nasal polyp tissues that present a combination of epithelium, mesenchyme, and vascular endothelium, with frequent massive hemopoietic infiltration. Anti-betaA-chain antibodies strongly stained epithelial mucous glands and some endothelial cells, and diffusely stained the polyp stroma. Normal adult conchae were similarly stained, whereas activin A was not detected prenatally by immunostaining of nasal tissues. Staining specificity was substantiated by ligand competition assays. Detailed examination of the inflammatory polyp infiltrate showed that activin A staining was reduced in sites of focal infiltration of B-lymphoid cells. It is therefore implied that local accumulation of a large number of B-cells is associated with relatively low activin A expression.

Activins↗

PubMed2001

Patterns of protein kinase C isoenzyme expression in transitional cell carcinoma of bladder. Relation to degree of malignancy.

We determined the pattern of protein kinase C (PKC) isoform expression in human cell lines by Western blotting and immunofluorescent staining techniques. In addition, we examined PKC isoform expression in tissue samples of transitional cell carcinoma (TCC) of the bladder. PKC delta, PKC beta II, and PKC eta were found primarily in the RT4 cell line (low-grade tumor), and PKC zeta was expressed most strongly in the SUP cell line (invasive tumor). In tissue samples of urinary bladder cancer, PKC isoenzymes were expressed differentially as a function of tumor stage and grade; expression of PKC beta II and PKC delta was high in normal tissue and in low-grade tumors and decreased with increasing stage and grade of TCC. The opposite pattern was seen with PKC zeta. The differences in expression of specific isoenzymes as related to levels of malignancy of the cell lines and tissue samples suggest that the PKC family has an important role in normal and neoplastic urothelium.

Blotting, Western↗

PubMed2001

Safety and immunogenicity of a new mammalian cell-derived recombinant hepatitis B vaccine containing Pre-S1 and Pre-S2 antigens in adults.

BACKGROUND: Previous data showed that new recombinant hepatitis B virus vaccine, which contains the S-protein component of the HBV surface together with the Pre-S1 and Pre-S2, is considerably more immunogenic than a second-generation recombinant HBV vaccine. OBJECTIVES: To compare the immunogenicity and safety of a novel recombinant HBV vaccine S1, Pre-S1 and Pre-S2 protein components of the hepatitis B surface antigen--BioHep, 10 micrograms dose, to a licensed vaccine containing only the S-protein component--Engerix-B, 20 micrograms dose. METHODS: A prospective randomized study included 524 adults--260 in the Bio-Hep group and 264 in the Engerix-B group. Both vaccines were administered in a three-dose regimen given at 0, 1 and 6 months, and adverse events were recorded on a diary card 5 days after each vaccination. Immunogenicity was tested by measuring anti-hepatitis B surface antibody. RESULTS: One month after the third injection, 98% of the BioHep subjects were found to be seroprotected vs. 85.1% of the Engerix-B group. In addition, the geometric mean titers were 2,203 mIU/ml and 326 mIU/ml in the Bio-Hep-B and Engerix-B groups respectively. An immunogenic advantage of Bio-Hep-B was suggested by the rapid onset of antibody response--66.5% were seroconverted one month after the first injection as compared to 19.3% in the Engerix-B group. No unexpected adverse events were observed, and the recorded events were mild in both groups. CONCLUSIONS: BioHep, a novel recombinant HBV vaccine containing S, Pre-S1 and Pre-S2 protein components, at a lower dose, is safe and more immunogenic than the conventional HBV vaccine that contains only S protein.

Adolescent↗

PubMed2000

Novel breast-tumor-associated MUC1-derived peptides: characterization in Db-/- x beta2 microglobulin (beta2m) null mice transgenic for a chimeric HLA-A2.1/Db-beta2 microglobulin single chain.

The MUC1 protein was found to be up-regulated in a spectrum of malignant tumors. T-cell responses to the MUC1 extracellular tandem repeat array (TRA) were observed in murine models as well as in breast-carcinoma patients. In the present study, we evaluated the anti-tumor potential of HLA-A2.1-motif-selected peptides from non-TRA domains of the molecule. Peptide immunogenicity was examined in the Db-/- x beta2 microglobulin (beta2m) null mice transgenic for a modified HLA-A2.1/Db-beta2 microglobulin single chain (HHD mice). Our results show the existence of 3 novel HLA-A2.1-restricted MUC1-derived cytotoxic T-lymphocyte (CTL) epitopes. These peptides are processed and presented by the HHD-transfected breast-tumor cell line MDA-MB-157. Moreover, CTL induced by these 3 peptides show higher lysis of target cells pulsed with breast-carcinoma-derived peptides than of targets pulsed with normal breast-tissue-derived peptides. These data suggest an important role for non-TRA MUC1-derived peptides as inducers of a MHC-restricted CTL reaction to a breast-carcinoma cell line and patient-derived tumor extracts.

Animals↗

PubMed2000

Overexpression of cyclin D1 mRNA in colorectal carcinomas and relationship to clinicopathological features: an in situ hybridization analysis.

Increased expression of a key cell cycle regulator, cyclin D1, may have relevance to carcinogenesis and clinicopathological characteristics of some cancers. This study represents the first application of in situ hybridization, ISH, to detect cyclin D1 mRNA in tissue sections from colorectal carcinomas. This approach was selected because of its unique potential to clarify whether increased expression of cyclin D1 mRNA correlates with clinical and pathological parameters. The ISH ofa non-radioactive oligonucleotide probe (Biogenex) was immunocytochemically detected in paraffin embedded sections from biopsy or resection specimens. Tumors ranged from well to poorly differentiated, and from stages A, B, C, and D. Ten year survival data were available on the majority of patients. Intensity of tumor and background (smooth muscle) signals were independently scored from 0 to 3. Overexpressed cyclin D1 mRNA was seen in 86% of cases compared to background. This frequency is similar to that reported for pancreatic carcinoma. The average signal intensity score in tumor foci was 1.9 with a background score of 0.05 (p<001). All cases showed specific staining judged by the cytoplasmic localization and a tumor signal:background ratio >1. Expression did not differentiate cancers based on grade, stage or survival (p>1), but did differentiate carcinoma and severe dysplasia from mild dysplasia. We conclude that ISH of cyclin D1 mRNA is an effective and relatively specific means of detecting activity of this gene in colonic neoplasms. The high frequency of overexpression implies that gene activity by itself is not likely to predict a tumor s biological or clinical behavior. On the other hand, these data suggest that increased cyclin D1 gene activity may be an early event in colorectal carcinogenesis. They also are consistent with findings showing cyclin D1 is inducible by a variety of oncogene products.

Adenocarcinoma↗

PubMed2000

Clinicopathologic study and classification of vocal cord cysts.

Cysts of the true vocal cords are less common than other laryngeal cysts. They are usually easily recognized and managed. Patients present with complaints of hoarseness and/or dyspnea. We report our experience with 41 cases of cysts located in the true vocal cords. Clinical and histological aspects are reviewed and discussed. A new histological classification is proposed: A: cysts lined by columnar epithelium with mucous content; B: lined by columnar epithelium with cilia; C: lined b squamous epithelium without keratinization; D: lined by squamous epithelium with keratinization.

Adult↗

PubMed2000

Synergistic anticancer activity of 1,25-dihydroxyvitamin D(3) and immune cytokines: the involvement of reactive oxygen species.

It was previously shown that 1,25-dihydroxyvitamin D(3) (1, 25(OH)(2)D(3)) enhances the cytotoxic activity of tumor necrosis factor alpha (TNFalpha), doxorubicin and menadione. A feature shared by these anticancer agents is the involvement of reactive oxygen species (ROS) in their action. In this work we found that 1, 25(OH)(2)D(3) acted synergistically with interleukin 1 beta (IL-1beta) or interleukin 6 (IL-6) to inhibit the proliferation of MCF-7 breast cancer cells. The extent of the synergism was maximal at 1 nM, a concentration at which 1,25(OH)(2)D(3), acting singly, only marginally reduced the cell number. The thiol antioxidant, N-acetylcysteine (NAC) abolished the synergism between IL-1beta or IL-6 and 1,25(OH)(2)D(3), but had only a small protective effect when the cytokines acted alone. NAC and reduced glutathione (GSH) protected MCF-7 cells from cytotoxicity induced both by TNFalpha alone and by TNFalpha and 1,25(OH)(2)D(3). A two-day exposure to TNFalpha caused a 27.7+/-3.1% (mean +/- SEM) reduction in GSH content. This effect increased to 46.4+/-5.5% by co-treatment with 1, 25(OH)(2)D(3) which did not affect GSH levels on it own. We conclude that 1,25(OH)(2)D(3) can act synergistically with anticancer cytokines present in the tumor milieu and that ROS plays a mediatory role in this interaction.

Acetylcysteine↗

PubMed2000

Differences in histochemical characteristics of gingival collagen after ER:YAG laser periodontal plastic surgery.

OBJECTIVE: The aim of this study is to evaluate gingival collagen for the effect of treatment with the Erbium:YAG Kesler handpiece. The handpiece is designed for gingival resurfacing in cases of hypertrophic gingiva and gingival pigmentation. BACKGROUND DATA: Lasers represent recent technological advances that afford new options for the treatment of periodontal diseases. However, lasers used for esthetic gingival soft tissue resurfacing require careful histopathological evaluation of the effects on tissue. In particular, it is important to determine the effect of laser irradiation on connective tissue, especially the collagen fibers. To date, no stage-wise clinical or histological studies have been performed addressing this issue. METHODS: Ten patients underwent irradiation with the following parameters: energy per pulse, 500 mJ; repetition rate, 10 pps; spot size, 3 mm. Gingival biopsy specimens were derived from 6 patients with hypertrophic gingiva and 4 with gingival pigmentation. The patients were examined before laser treatment and at 7 and 14 days after laser treatment. The tissues were fixed in tymph node revealing solution (LNRS), embedded in paraffin, sectioned at 5 microm, and stained with hematoxylin & eosin. The status of collagen in the treatment site was examined under polarized light after picrosirius red (PSR) staining. PSR is a collagen stain that differentiates collagen fiber density or size by means of a spectrum of color changes under polarized light. The major colors are red, orange, yellow, and green. RESULTS: We found a significant difference in the properties of collagen fibers at the first week and at 14 days post-treatment. In the normal gingiva, the predominant polarization colors were in the red-orange range, signifying tightly packed, mature collagen. During the first postoperative week, collagen fibers exhibited polarization colors in the green to green-yellow range, implying loosely packed collagen fibers. After 2 weeks, collagen fibers reacquired their preoperative PSR characteristics. CONCLUSIONS: We conclude that sequential series of changes accompany photothermal treatment of the gingiva. The occurrence of this sequence in all successful outcome cases may suggest the importance of these temporally sequenced changes in collagen during gum healing. In any event, the status of PSR staining of gum collagen provides a useful adjunct in the assessment of gingival health.

Adult↗

PubMed2000

The value of early and double phase 99Tcm-sestamibi scintimammography in the diagnosis of breast cancer.

The aim of this study was to assess the additional value of early and double phase scintimammography (SMM) with 99Tcm-sestamibi in the detection of breast cancer following initial evaluation by palpation and mammography. Altogether, 322 women with breast lesions evaluated prospectively by palpation, fine-needle aspiration and mammography were assigned a malignancy risk according to the results. Scintimammography was performed in all patients in the prone breast dependent position. Immediate and delayed views were obtained. Acquisition of immediate tracer uptake was termed 'early phase' SMM, whereas a combination of both immediate and delayed phase images was termed 'double phase' SMM. All patients underwent breast biopsy. Both early phase and double phase SMM detected eight of nine tumours in the low-risk group (88.8% sensitivity). In the uncertain cases (moderate-risk group), early phase SMM detected all malignant tumours, but double phase SMM missed one (92.3% sensitivity). In the high-risk group, early phase SMM missed two breast cancers (94.6% sensitivity) and double phase SMM missed four (89.2% sensitivity). Overall, early phase SMM had a sensitivity of 94.9% and a specificity of 80.2% in detecting breast cancer, whereas double phase SMM had a sensitivity of 89.8% and a specificity of 94.3%. Both methods had 100% sensitivity for tumours larger than 1 cm. In conclusion, SMM detected additional breast cancers following an initial evaluation by palpation, fine-needle aspiration and mammography. Our results suggest that double phase SMM is more specific than early phase SMM, although early phase SMM is more sensitive. Whether the interpretation of SMM results should rely on both early and delayed images, or early images alone, should be based on the relative risk of malignancy of the breast lesion as estimated by the initial evaluation.

Adult↗

PubMed2000

Protein kinase C (PKC) isoenzymes immunohistochemistry in lymph node revealing solution-fixed, paraffin-embedded bladder tumors.

Protein kinase C (PKC) plays an important role in cellular differentiation and in the malignant process. In an earlier study, it was shown that the expression pattern of PKC isoenzymes is altered in some tumors compared to their corresponding normal tissue. In this study, we evaluated the pattern of PKC isoenzyme immunostaining in bladder transitional cell carcinoma (TCC) of different grades and stages and normal tissue. Twenty-seven TCC samples and six areas of normal bladder mucosa were stained with antibodies specific for the PKC isoenzymes: alpha, beta 1, beta 2, delta, and zeta. The sections were scored for intensity of staining, and the correlation with grade and stage of the tumors was computed. The PKC alpha and beta 2 immunostains were intense in normal urothelium and in all evaluated tumors. PKC beta 1 and delta stains were intense in normal and low-grade and -stage tumors and weak in high-grade and -stage tumors. The opposite trend was found for PKC zeta. PKC isoenzyme expression differs in invasive TCC compared to low-grade, low-stage TCC and normal urothelium. The value of these findings as a marker of tumor aggressiveness should be further assessed.

Aged↗

PubMed2000

A comparison of two dose regimens in pancreatic cancer.

Forty-seven patients with pancreatic cancer were treated with two different schedules of 5-fluorouracil (5FU) and leucovorin (LCV): standard and dose-intense schedules. The standard regimen was monthly and the dose intense was biweekly. Partial response was observed in one patient (4%), no change in 12 (48%) and progression of disease in another 12 patients. Clinical benefit, measured by symptomatic improvement, was observed in 19% of all the patients, in 12% of those treated with the standard regimen and in 27% of the intense group. Median survival was 8 months for all the patients. The 1-year survival rate was 32%. Toxicity was mild. There was no survival benefit for the dose intense regimen. These results indicate that clinical benefit can be obtained with 5FU and LCV regimens despite the lack of objective response and that a dose-intense schedule is of little benefit in treating pancreatic cancer.

Adult↗

PubMed2000

Black thyroid adenoma. Clinical, histochemical, and ultrastructural features.

A 22-year-old woman with a "hot" thyroid nodule who was being treated with minocycline for severe acne vulgaris is presented. A partial thyroidectomy specimen revealed a black adenoma. Microscopically, the black pigment was found in the follicular cells and the colloid of the adenoma. The pigment was bleached with potassium permanganate and was Fontana-Masson stain positive. It was negative for iron, periodic acid-Schiff, and acid-fast Ziehl-Neelsen stains. All these feature suggest a melanin-like pigment. However, electron microscopic examination revealed a dense osmophilic material present within the lysosomes of the follicular cells. No melanosomes were present. Twenty-six previously reported cases are reviewed, and the possible mechanisms for the deposition of the pigment in the adenoma and its relation to minocycline degradation products are discussed.

Acne Vulgaris↗

PubMed1999

1,25-Dihydroxyvitamin D3 enhances the susceptibility of breast cancer cells to doxorubicin-induced oxidative damage.

1,25-Dihydroxyvitamin D3 (1,25(OH)2D3), the hormonal form of vitamin D, has anticancer activity in vivo and in vitro. Doxorubicin exerts its cytotoxic effect on tumor cells mainly by two mechanisms: (a) generation of reactive oxygen species (ROS); and (b) inhibition of topoisomerase II. We studied the combined cytotoxic action of 1,25(OH)2D3 and doxorubicin on MCF-7 breast cancer cells. Pretreatement with 1,25(OH)2D3 resulted in enhanced cytotoxicity of doxorubicin. The average enhancing effect after a 72-h pretreatment with 1,25(OH)2D3 (10 nM) followed by a 24-h treatment with 1 microg/ml doxorubicin was 74+/-9% (mean +/- SE). Under these experimental conditions, 1,25(OH)2D3 on its own did not affect cell number or viability. 1,25(OH)2D3 also enhanced the cytotoxic activity of another ROS generating quinone, menadione, but did not affect cytotoxicity induced by the topoisomerase inhibitor etoposide. The antioxidant N-acetylcysteine slightly reduced the cytotoxic activity of doxorubicin but had a marked protective effect against the combined action of 1,25(OH)2D3 and doxorubicin. These results indicate that ROS are involved in the interaction between 1,25(OH)2D3 and doxorubicin. 1,25(OH)2D3 also increased doxorubicin cytotoxicity in primary cultures of rat cardiomyocytes. Treatment of MCF-7 cells with 1,25(OH)2D3 alone markedly reduced the activity, protein, and mRNA levels of the cytoplasmic antioxidant enzyme Cu/Zn superoxide dismutase, which indicated that the hormone inhibits its biosynthesis. This reduction in the antioxidant capacity of the cells could account for the synergistic interaction between 1,25(OH)2D3 and doxorubicin and may also suggest increased efficacy of 1,25(OH)2D3 or its analogues in combination with other ROS-generating anticancer therapeutic modalities.

Antineoplastic Agents↗

PubMed1999

Lymph node revealing solution: a rapid method for the fixation of cystectomy specimens.

The objective of this study was to describe the use of the lymph node revealing solution (LNRS) for rapid fixation of total cystectomy specimens, and to compare it with formalin fixation. LNRS is a mixture of 95% ethanol, diethyl ether, glacial acetic acid and buffered formalin (65:20:5:10 v/v) prepared under a fume-hood. Sixteen consecutive cystectomy specimens were fixed for two hours either in LNRS or in buffered formalin. Representative sections were embedded in paraffin, sectioned and stained with H&E, periodic acid Schiff, alcian-blue, and immunostained for cytokeratins 20, high and low molecular weight cytokeratins, prostatic specific antigen, Factor VIII related antigen, s-100 protein, and protein kinase C isoenzymes. Results showed that the tissues were well fixed after 2 hours in LNRS, and were not fixed after 2 hours in formalin. Processing and sectioning of the paraffin blocks of the LNRS fixed tissue was excellent; it was impossible in the sections fixed for 2 hours in formalin. All the stains were excellent after LNRS fixation. We conclude that fixation of cystectomy specimens in LNRS requires only two hours and results in excellent stained slides. It is therefore recommended for cystectomy specimens.

Biomarkers, Tumor↗

PubMed1999

A new rapid technique for the fixation of thyroid gland surgical specimens.

One of the main diagnostic problems in thyroid pathology is to distinguish between follicular adenoma and follicular carcinoma. Thorough sampling of the nodule's capsule is recommended in order to identify capsular invasion. However, during the hardening of the tissue, by the usual fixatives the capsule shrinks and rolls downwards and sometimes the capsule separates from the remaining tissue. The present work evaluates the use of "Lymph Node Revealing Solution" (LNRS) for the rapid fixation (2h) of different thyroid lesions as compared to that of formalin. Fifty-one unselected consecutive cases of thyroid nodules, which included various benign and malignant lesions, were examined. Each specimen was cut in two equal parts; one was fixed in LNRS, the other in formalin. Fixation in LNRS for 2 hours gave adequate results in sectioning and staining of the tissue, and excellent immunostains. Its advantage over formalin is the conservation of the natural relationship between the capsule and the rest of the tissue, on the same plane, as well as the short time required for the final diagnosis.

Acetic Acid↗