In Vivo Imaging of the Buccal Mucosa Shows Loss of the Endothelial Glycocalyx and Perivascular Hemorrhages in Pediatric Plasmodium falciparum Malaria.

Severe malaria is mostly caused by Plasmodium falciparum, resulting in considerable, systemic inflammation and pronounced endothelial activation. The endothelium forms an interface between blood and tissue, and vasculopathy has previously been linked with malaria severity. We studied the extent to which the endothelial glycocalyx that normally maintains endothelial function is involved in falciparum malaria pathogenesis by using incident dark-field imaging in the buccal mucosa. This enabled calculation of the perfused boundary region, which indicates to what extent erythrocytes can permeate the endothelial glycocalyx. The perfused boundary region was significantly increased in severe malaria patients and mirrored by an increase of soluble glycocalyx components in plasma. This is suggestive of a substantial endothelial glycocalyx loss. Patients with severe malaria had significantly higher plasma levels of sulfated glycosaminoglycans than patients with uncomplicated malaria, whereas other measured glycocalyx markers were raised to a comparable extent in both groups. In severe malaria, the plasma level of the glycosaminoglycan hyaluronic acid was positively correlated with the perfused boundary region in the buccal cavity. Plasma hyaluronic acid and heparan sulfate were particularly high in severe malaria patients with a low Blantyre coma score, suggesting involvement in its pathogenesis. In vivo imaging also detected perivascular hemorrhages and sequestering late-stage parasites. In line with this, plasma angiopoietin-1 was decreased while angiopoietin-2 was increased, suggesting vascular instability. The density of hemorrhages correlated negatively with plasma levels of angiopoietin-1. Our findings indicate that as with experimental malaria, the loss of endothelial glycocalyx is associated with vascular dysfunction in human malaria and is related to severity.

Angina bullosa haemorrhagica-like lesions in pemphigus vulgaris.

BACKGROUND/OBJECTIVES: The aim of this study was to describe a previously unreported association of oral pemphigus vulgaris with short-lived blood-filled painless blisters resembling angina bullosa haemorrhagica (ABH). METHODS: A cross-sectional study of consecutive patients with Pemphigus vulgaris. All patients were examined for the presence of ABH-like lesions, and demographic, clinical and histopathological data were collected. Histopathological examination was performed when feasible. RESULTS: A total of 318 with pemphigus vulgaris were included (63.5% female, mean age: 46 years). ABH-like lesions were present in 82 (25.8%) patients, commonly observed in the buccal mucosa (47, 57.3%) followed by the palate (15, 18.3%). All patients had normal platelet counts with no evidence of bleeding diathesis. Biopsies of the ABH-like lesions showed suprabasal clefts in four of six samples. ABH-like lesions were significantly associated with partial remission of pemphigus vulgaris (47.5%, P = 0.002) and the use of intraoral steroids (P = 0.001, odds ratio: 5.9 [95% confidence interval: 2.5-13.6]). CONCLUSION: ABH-like lesions may represent a transient or abortive form of oral pemphigus vulgaris and tend to have a benign and self-limiting nature.

Exfoliative cytology of the oral mucosa: comparison of two collection methods.

This study compared the sampling efficacy of a cytobrush and metal spatula for exfoliative cytology of the oral mucosa. Thirty students with no detectable oral alterations upon clinical examination were submitted to exfoliative cytology of the lateral border of the tongue, using a metal spatula on the left side and a cytobrush on the right side. The smears were stained using the Papanicolaou technique and evaluated for cellularity, cell type, cell distribution, homogeneity, and cellular distortion, as well as the presence of mucus, inflammatory infiltrate, and hemorrhage. A statistical test (Z-test) with a 95% confidence interval (CI) showed a significant difference between the metal spatula and cytobrush in terms of cellularity (p = 0.02) and homogeneity (p = 0.01). No difference between the two methods was observed regarding cell type (p = 0.4, Z-test) or cell distribution for the 95% confidence interval (p = 0.2, Fisher's test). Cell distortion and the presence of mucus were observed in five cases that used the metal spatula and in two cases that used the cytobrush. No hemorrhage or inflammatory infiltrate was detected in any of the slides. Based on the results of this study, the cytobrush produced qualitatively better smears in terms of cellularity and homogeneity compared to the metal spatula.

Factitious lip crusting.

Four cases of factitious crusting of the lips in women are reported. Two of the women had hemorrhagic crusts, and two had keratotic yellow crusts. All four patients had personality disturbances. Biting, picking, or unconscious licking of the lips may be the underlying mechanism for trauma and crust formation. This entity should be distinguished from contact cheilitis, actinic cheilitis, infectious cheilitis glandularis, and cheilitis granulomatosa. Some cases of exfoliative cheilitis may also be factitious. The presence of bizarre hemorrhagic or keratotic crusts on the lips should alert the clinician to a possible factitious origin, and a psychiatric evaluation should be done.

Alveolar soft-part sarcoma of the tongue.

Alveolar soft-part sarcoma is a rare, aggressive malignancy of uncertain histologic origin with a propensity for vascular invasion and distant metastasis. This neoplasm may mimic benign vascular neoplasms or malformations but careful evaluation of the unique imaging features on CT scans, MR images, and angiograms lead to the correct diagnosis. We present a case of alveolar soft-part sarcoma of the tongue and emphasize its radiologic and clinical features.

Upper airway obstruction secondary to warfarin-induced sublingual hematoma.

Sublingual hematoma is a rare but potentially fatal complication of oral warfarin sodium. Less than ten cases are reported in the English-language literature with only two of these appearing in the otolaryngologic literature. Spontaneous bleeding into the sublingual and submaxillary spaces creates a "pseudo-Ludwig's" phenomenon with elevation of the tongue and floor of mouth and subsequent airway compromise. Two new cases, along with a review of the literature are presented. Management is directed at prompt control of the airway and reversal of the coagulopathy. Sore throat is a uniform, early complaint that should be taken seriously in any patient receiving oral anticoagulation therapy.

Histologic comparisons of interproximal gingival tissues related to the presence or absence of bleeding.

Interproximal gingival tissues were compared histologically relative to the presence or absence of bleeding after stimulation with a wooden interdental cleaner. Fifteen bleeding and 15 nonbleeding interproximal gingival biopsy specimens were obtained from 30 patients and processed for light microscopic evaluation. Morphometric analysis of tissue components revealed that bleeding areas had a significantly greater per cent of inflamed connective tissue. The inflammatory lesion in the bleeding specimens was primarily in the midinterproximal area. From a diagnostic standpoint, this information provides a rationale for the use of bleeding to detect inflammatory lesions in the midinterproximal region.

Depth of periodontal probe penetration related to clinical and histologic signs of gingival inflammation.

The purpose of this study was to determine if the depth of periodontal probe penetration into the gingival sulcus was related to bleeding after probing with a standardized force, visual signs of gingival inflammation, and histological parameters of gingival inflammation. Sixty midfacial gingival sites in 26 persons were evaluated for presence or absence of visible inflammation and bleeding after probing using a controlled insertion pressure of 25 gm. In order to delineate the area for histologic analysis, a reference incision was made on the facial surface of the gingiva which corresponded to the depth and mesio-distal extent of the area probed and evaluated for visual signs of inflammation. Gingival biopsy specimens were histometrically analyzed to determine the depth of probe penetration and percentage of inflamed connective tissue. Statistical analysis of the data demonstrated that probe penetration was significantly greater in the presence of visible inflammation, but not with bleeding after probing. Furthermore, only a weak correlation existed between depth of probe penetration and percentage of inflamed connective tissue adjacent to the area probed.

Associations between bleeding and visual signs of interdental gingival inflammation.

Interdental gingival tissues are designated inflamed on the basis of their color and bleeding after stimulation. Gingival bleeding was previously shown in histological studies to indicate the presence of inflammatory lesions. The present study was undertaken to determine associations between bleeding and visual signs of interdental gingival inflammation. Each interdental site in 82 males, aged 18 to 30, was evaluated for the presence or absence of visual signs of inflammation. The interdental sites on one side of the mouth were evaluated for bleeding tendency using the Papilla Bleeding Index (PBI), while the other half was evaluated using the Eastman Interdental Bleeding Index (EIBI). The percentage of inflamed areas detected with the EIBI and visual method was similar and significantly higher than with the PBI. When the visually noninflamed sites were examined, 38.5% of these areas bled, indicating that interdental inflammatory lesions existed in the absence of visual signs of inflammation. Of the sites that bled but were visually noninflamed, 33.1% were detected using the PBI, while 66.9% were detected using the EIBI. The Eastman Interdental Bleeding Index was a more reliable clinical indicator for detecting interdental inflammatory lesions than the Papilla Bleeding Index.

Histologic characteristics associated with bleeding after probing and visual signs of inflammation.

This study was designed to characterize histologically the gingival lesion associated with visual signs of inflammation and bleeding after probing. Sixty midfacial gingival sites in 26 persons were evaluated for visual presence of absence of inflammation and bleeding after probing using a controlled insertion pressure of 25 gm. In order to delineate the area for histologic analysis, a reference incision was made on the facial surface of the gingiva which corresponded to the depth and mesio-distal extent of the area probed and evaluated for signs of inflammation. Gingival biopsy specimens were morphometrically analyzed to determine the percentages of cell rich--collagen poor connective tissue and blood vessel lumens. Histometric data were grouped and compared with respect to the presence or absence of inflammation and bleeding. Specimens associated visually with inflammation had significantly greater percentages of both cell rich--collagen poor connective tissue and blood vessel lumens. Bleeding upon probing was associated with a significantly greater percentage of cell rich--collagen poor connective tissue without an increase of blood vessel lumens. It was concluded that both observed signs of inflammation and bleeding after probing can be used to detect inflammatory lesions in the gingiva. However, in areas inaccessible for evaluation of inflammation, bleeding determinations using controlled insertion pressures provided an objective diagnostic method for detecting the presence of an inflammatory lesion.

Cell populations associated with gingival bleeding.

The presence of crevicular bleeding after probing is an objective clinical sign of gingival inflammation. It has been associated with a plasma cell-dominated inflammatory infiltrate in deep pockets and has been suggested as an indication of active periodontitis. The purpose of this study was to characterize the cellular composition of gingival connective tissue associated with shallow pockets which bled after probing. Prior to biopsy, the mid-facial gingiva associated with 30 teeth from 26 patients was assessed for the presence or absence of visual inflammation, pocket depth and bleeding after probing with a standardized force of 25 g. A horizontal reference incision was made on the facial aspect of the gingiva to demarcate for histologic analysis the specific gingival area probed and evaluated for inflammation. Cell populations were determined from histological sections using morphometric point counting techniques in six standard fields at and coronal to the level of the reference incision. The percentage of cell types and the per cent volume densities of all tissue components were compared between clinically normal and inflamed gingiva. In clinically inflamed gingiva there was a significantly greater percentage of lymphocyte/macrophage/monocyte cells and a smaller percentage of fibroblast/endothelial cells. The percentage of plasma cells was only a fraction of that found for other inflammatory cells. The results of this study indicated that a lesion in the gingiva associated with bleeding after probing can consist of an inflammatory infiltrate which is not dominated by plasma cells.

Cell populations associated with conversion from bleeding to nonbleeding gingiva.

The purpose of this study was to observe changes in cell populations of the interdental gingival tissue, which accompanied the conversion of a bleeding to a nonbleeding state induced by scaling and improved oral hygiene. Fifteen bleeding and 18 stopped-bleeding interproximal gingival biopsies were obtained from 33 patients and processed for light microscopic evaluation. The morphometric analysis of eight connective tissue components revealed that the percentage volume density of all inflammatory cells decreased, and the percentage of fibroblasts and collagen increased, when the gingiva changed from a bleeding to a nonbleeding state. Furthermore, the inflammatory cell infiltrate in bleeding and stopped-bleeding specimens was dominated by mononuclear cells of the lymphocyte/macrophage/monocyte group, while plasma cells and polymorphonuclear leukocytes comprised only a small fraction of the inflammatory cells present. Significant repair of gingival connective tissue had occurred in the stopped-bleeding specimens.

Histological characteristics associated with suppurating periodontal pockets.

The purpose of this study was to characterize histologically the gingival lesion associated with suppuration in advanced periodontitis. Thirty-three bleeding, suppurating (S) and 23 bleeding, nonsuppurating (NS) interproximal biopsies were obtained from nine patients and processed for light microscopy. Pocket depths (mean +/- SD) were 6.7 +/- 1.6 mm (S) and 5.4 +/- 2.2 mm (NS). Six-micron serial sections were stained with (1) hematoxylin/eosin and (2) van Gieson. Quantitative cell types were determined by a grid intersection counting technique at x 1000. Volumetric analysis of collagen-poor (inflammation) areas was conducted using a computer biometric system that revealed three histologic patterns: Type I sites showed mild to moderate inflammation (less than 50% infiltrate, S = 15, NS = 20); Type II sites showed intense inflammation (greater than 50% infiltrate, S = 17, NS = 3); and only one (S) site had a large connective tissue abscess (Type III). The mean percentage of collagen-poor area was significantly larger in suppurating (42.1 +/- 25.5%) versus nonsuppurating (27.7 +/- 20.4%) sites (P = 0.02). In both S and NS sites, plasma cells (means = 66%) and lymphocytes (means = 27%) predominated in the inflammatory infiltrates. Histologically, suppuration appeared to be associated with increased gingival inflammation and a slight increase in connective tissue neutrophils.

Effect of personal oral hygiene on bleeding interdental gingiva. Histologic changes.

A previous study demonstrated that the combination of subgingival scaling and improved oral hygiene resulted in a reduction of clinical and histological signs of interdental gingival inflammation, changes that were associated with a cessation of interdental gingival bleeding. The present study compared, histologically, the interdental tissues of bleeding sites with sites that initially bled but had been converted to nonbleeding by an oral hygiene program alone. Morphometric analysis of interdental gingiva demonstrated that conversion from bleeding to nonbleeding was associated with a significant reduction in the inflamed connective tissue component. This study showed that an oral hygiene program consisting of toothbrushing and interdental cleaning could significantly reduce interdental inflammation, and that bleeding determinations monitored the effects of this therapy.

Responses of four tooth and site groupings to periodontal therapy.

The responses of four tooth/site groupings to periodontal therapy were evaluated. Eighty-two patients with periodontitis were treated in a split mouth design with coronal scaling, root planing, modified Widman surgery, and flap with osseous resectional surgery. Patients were evaluated prior to therapy, 4 weeks post-Phase I therapy, 10 weeks post-Phase II therapy, and at yearly intervals during 2 years of maintenance therapy. The tooth/site groupings evaluated were: 1) interproximal sites of single rooted teeth (T1), 2) facial and lingual sites of single rooted teeth (T2), 3) nonfurcation sites of molar teeth (T3), and 4) furcation sites of molar teeth (T4). Following 2 years of maintenance, no clinically significant differences in probing depth reduction or probing attachment loss were present between the four tooth/site groupings in 1 mm to 4 mm sites. T2 had the greatest decrease of probing depth in 5 mm to 6 mm sites followed by T1, T3 and T4. T1 and T2 showed a greater gain of probing attachment followed by T3 and T4. T1 and T2 had the greatest decrease of probing followed by T3 which was greater than T4 in greater than or equal to 7 mm sites. T4 had significantly less probing attachment gain than the other groups. There was a trend for T1 and T2 to have less gingival bleeding post-therapy and for T2 to have less plaque accumulation than the other groups at both pre- and post-therapy examinations.

Significance of haemorrhages in central parts of the tongue found in the medicolegal autopsy.

The tongue was examined for the presence of haemorrhages in 264 medicolegal autopsy cases. The tongue was sectioned transversely and examined macroscopically and microscopically. Haemorrhages were found in marginal and/or central parts of the tongue in 104 cases. Among them, 28 cases showed haemorrhages in central parts of the tongue. Those haemorrhages in central parts of the tongue were seen only in cases of severe 'congestive death'. The possibility must therefore be considered of a severe 'asphyxial death', if haemorrhages are found in central parts of the tongue during autopsy.

Photofrin-mediated photodynamic therapy of chemically-induced premalignant lesions and squamous cell carcinoma of the palatal mucosa in rats.

Photodynamic therapy (PDT), an experimental cancer therapy, was studied in an animal model of chemically-induced epithelial dysplasia and squamous cell carcinoma. PDT was performed 24 hours after i.v. injection of 2.5 mg/kg bw Photofrin, and using 100 J/cm2 incident light at two activation wavelengths (514.5 nm or 625 nm). Two days after PDT, the majority of rats macroscopically showed a marked erythema of the entire palatal region. Microscopically all the rats showed oedema, haemorrhage, and necrosis of the epithelium of the intermolar area. The long-term results were not so favourable. No evidence of disease was found in 6 out of 20 rats in the 514.5 nm group and in 2 out of 20 rats in the 625 nm treated group. Epithelial dysplasia was found in 14 out of 20 rats in the 514.5 nm group, and in 18 out of 20 rats of the 625 nm treated group. Squamous cell carcinomas were found in 4 out of 20 rats treated with 514.5 nm and in 7 out of 20 rats in the 625 nm treated groups. Comparing both treatment wavelengths, better results were obtained in the 514.5 nm groups as this wavelength gave less normal tissue damage. Based on the results of this study the application of PDT for the treatment of field cancerization and squamous cell carcinoma of the oral cavity, is discussed.

Angina bullosa hemorrhagica.

Angina bullosa hemorrhagica is characterized by acute blood blisters, mainly on the soft palate. Elderly patients are usually affected and lesions heal spontaneously without scarring. The pathogenesis is unknown, although it may be a multifactorial phenomenon. Trauma seems to be the major provoking factor and long term use of steroid inhalers has also been implicated in the disease. No underlying hematologic or immunopathogenic disorder has been found. Treatment is symptomatic. We present a 67-year-old patient with recurrent oral blood blisters which were diagnosed as angina bullosa hemorrhagica. Trauma by dental injections and use of steroid inhalers were identified as etiologic factors in this case. Erosions healed with a week. Although this is a benign condition, it may result in acute airway obstruction. Recognition is, therefore, of great importance for dermatologists.