Clinical care in craniofacial microsomia: a review of current management recommendations and opportunities to advance research.

Craniofacial microsomia (CFM) is a complex condition associated with microtia, mandibular hypoplasia, and preauricular tags. It is the second most common congenital facial condition treated in many craniofacial centers and requires longitudinal multidisciplinary patient care. The purpose of this article is to summarize current recommendations for clinical management and discuss opportunities to advance clinical research in CFM.

[Surgical repair of type A aortic dissection with severe atherosclerosis; report of a case].

We report a case of type A aortic dissection with severe atherosclerosis. An 81-year-old man with acute type A aortic dissection was referred to our hospital. Computed tomography revealed DeBakey type II dissection with severe atherosclerosis. Ascending aortic replacement was performed urgently, and an autologous pericardium strip was placed in the lumen to prevent atheroembolization and to reinforce the friable atherosclerotic intima This technique was useful for avoiding cerebral vascular accidents. The patient was discharged on the 24th operative day with no complications.

Multidetector-row CT findings of colonic perforation: direct visualization of ruptured colonic wall.

BACKGROUND: We examined the findings of contrast-enhanced multidetector-row computed tomography (MD-CT) in patients with colonic perforation. METHODS: Abdominal contrast-enhanced MD-CT findings in six patients with colonic perforation were reviewed retrospectively. Patients (three men and three women) were 74 to 88 years old (mean age = 78 years). Colonic perforation was confirmed by surgery. CT findings were correlated with surgical and pathologic findings. RESULT: The site of colonic perforation was suggested by the following combination of CT findings: free air, dirty mass, dirty fat sign, extraluminal fluid collection, bowel wall thickening, and interruption of colonic wall. The ruptured colonic wall was directly visualized in four cases (67%). CONCLUSION: Abdominal contrast-enhanced MD-CT may improve the accuracy of diagnosis and localization of colonic perforation.

Down-regulation of decorin, a transforming growth factor-beta modulator, is associated with scarless fetal wound healing.

PURPOSE: Transforming growth factor beta (TGF-beta) bioactivity has been implicated as a potential regulator of the transition from scarless healing to scar formation in fetal wounds. Decorin is an extracellular matrix proteoglycan that regulates TGF-beta bioactivity and assists in collagen fibrillogenesis. To determine its role in scarless repair, the authors examined decorin expression in fetal fibroblasts, skin, and wounds. METHODS: A single, full-thickness, 2-mm open wound was created on the dorsal surface of fetal rats at 16.5 days (E16) and 18.5 days (E18) gestational age (term, 21.5 days [E21]). Wounds were harvested at 24 and 72 hours (n = 12 wounds per time-point). Nonwounded fetal skin at E17, E19, and E21 was harvested for analysis of decorin expression during skin development and as controls for wounds. In addition, fetal (E14, E18) and adult dermal fibroblasts were cultured for in vitro analysis. Reduced-cycle, specific primer, reverse transcriptase polymerase chain reaction was performed to quantitate decorin expression. RESULTS: Decorin expression increased rapidly with increasing gestational age in both fetal fibroblasts and skin. Expression was increased 22-fold in E18 fibroblasts (P <.002) and 300-fold in adult fibroblasts (P <.001) compared with E14 fibroblasts. In skin, expression increased 74% (P <.01) during the fetal wound healing transition period between E17 and E19. However, in E16 wounds (scarless), decorin expression decreased 59% (P <.006) at 24 hours and 45% (P <.02) at 72 hours. Decorin expression did not change in E18 (scar) wounds at 24 and 72 hours (P >.05). CONCLUSIONS: Early gestation fetal fibroblasts and fetal skin express decorin at lower levels than late gestation fetal and adult fibroblasts and skin. Decorin expression is down-regulated in scarless (E16) compared with scar (E18) wounds. Thus, increased decorin expression is associated with both skin development and scar formation. Conversely, decreased decorin expression is associated with scarless repair.

Comparative evaluation of screw configuration on the stability of the sagittal split osteotomy.

This study is a comparative evaluation of two commonly used screw configurations on the rigidity of the sagittal split osteotomy. A cadaver model was used to compare the immediate load strength of three screws placed horizontally above the neurovascular bundle (horizontal configuration) versus two screws placed horizontally above the bundle and one screw placed inferiorly below the bundle (triad configuration). The triad configuration was found to have a mean percentage increase in rigidity of 58% over the horizontal configuration. The paired t test was used to evaluate the data, disclosing a significant difference in load strength (p less than 0.01).

Monoclonal antibody to the streptococcal preparation OK-432: tissue OK-432 localization and analysis of interaction between OK-432 and macrophages or NK cells in human salivary adenocarcinoma-bearing nude mice given OK-432.

An immunoglobulin M mouse monoclonal antibody (MAb) to the streptococcal preparation OK-432, TS-1, was generated. The TS-1 antigen is a carbohydrate epitope. This antigen is stable upon fixation and embedding in paraffin. The tissue and cellular OK-432 localization in human salivary adenocarcinoma-bearing nude mice given OK-432 intratumorally was examined by various methods according to the immunological procedures using the purified TS-1 MAb. The presence of OK-432 antigen recognized by TS-1 MAb was clearly observed in the tumor as well as the spleen and lung 24 or 48 h after OK-432 administration, whereas transfer of OK-432 from the site of injection to the organs, such as liver and kidney, was rarely seen. The presence of OK-432 antigen in some immunocompetent cells, as defined by Mac-1 antigen or asialo GM1 antigen, was observed by the double-antibody labeling technique in the tumor and spleen from tumor-bearing nude mice. Moreover, interaction between OK-432 and macrophages or natural killer (NK) cells in relation to expression of interferon (IFN) in tumor-bearing nude mice given OK-432 was observed. Consequently, significant increases of Ia-positive or Ia-negative macrophages, NK cells as well as IFN-alpha/beta- or IFN-gamma-positive cells in the tumor and/or spleen were found when compared with those without OK-432 administration.

Effect of androgen on ornithine decarboxylase activity in androgen-dependent mouse mammary tumor (Shionogi Carcinoma 115) and its androgen-independent subline (CS 2).

The activity of ornithine decarboxylase in androgen-dependent mouse mammary tumor (Shionogi Carcinoma 115) was reduced to 25% by castration of tumor-bearing mice and restored to the normal level 12 h after administration of testosterone or 5 alpha-dihydrotestosterone. Administration of estradiol-17 beta to the tumor-bearing castrated mice also stimulated the enzyme activity while progesterone and cortisol had little effect. On the other hand, the enzyme activity was affected by neither castration nor androgen injection to CS 2, which is a subline of SC 115 and completely independent of androgen for growth. The inhibition of ornithine decarboxylase activity in SC 115 by injecting alpha-difluoromethylornithine did not affect the enhancement of RNA polymerase I activity by androgen, showing independent elevation of the levels of the two enzymes by androgen.

Interferon activity and its characterization in the sera of patients with premalignant lesions arising in oral mucosa.

The interferon (IFN) assay of the sera from the 26 patients with premalignant lesions such as lichen planus and leukoplakia arising in oral mucosa was performed by the plaque-reduction assay with vesicular stomatitis virus in FL cells derived from human amniotic membrane. When the serum IFN activity was characterized by acid treatment, significant increase of acid-stable IFN in the patients was found as compared with those in the normal controls. The titers of gamma-like IFN defined by anti-HuIFN-alpha and anti-HuIFN-beta in the sera of patients of 50-79 years age group (n = 17, P less than 0.002) showed a highly significant increase as compared with the relevant normal controls (n = 20). All of the 26 patients were treated with topical administration of HuIFN-beta. When the correlation between prognosis of the disease and titers of serum IFN was investigated by measuring gamma-like IFN and acid-stable IFN in the sera of patients, all of 13 patients with good prognosis after the HuIFN-beta therapy showed significantly decreased levels of gamma-like IFN (P less than 0.01), whereas the serum level of acid-stable IFN after HuIFN-beta therapy showed a significant increase compared to that before the therapy (P less than 0.05). These findings indicate that the endogenous IFN system may be associated with the pathophysiology in patients with the oral mucosal lesions.

Therapeutic effect of human fibroblast interferon on premalignant lesions arising in oral mucosa. A pilot study.

Human fibroblast interferon (HuIFN-beta) was topically administered to 20 premalignant lesions histopathologically showing epithelial dysplasia such as leukoplakia and lichen planus which arose in the oral mucosa. HuIFN-beta was prepared in the water-soluble gel form containing 2% carboxymethylcellulose, 45% glycelin, 0.1 M citrate buffer (pH 4.5) and 0.2% SDS as stabilizing agents. This preparation was found to be effective for herpetic gingivostomatitis and zostal lesions arising along the intercostal nerve. Thus, the HuIFN-beta preparation (10(4) to 5 X 10(3) IU) was applied to the oral mucosal lesion for 1 h twice a week. The lesion with topical administration of HuIFN-beta was covered tightly with the mucosal bandage which was coated with carboxymethylcellulose, glycelin and CaCl2 on vinyl acetate matrix. The 14 oral lesions with erosion or ulcer formation accompanied by severe pain by touch, had complete remission after approximately 10 successive applications of this preparation. Although subjective symptoms such as irritation pain in the other 6 patients with severe hyperkeratotic lesion subsided, white coatings and streaks could not be completely removed by this therapy. No other side-effects excluding slight pain and reddish swelling which occurred intermittently during HuIFN-beta administration were observed.

Interferon activity and its characterization in the sera of patients with head and neck cancer.

The interferon (IFN) assay of the sera from the 40 patients with head and neck cancer was performed by the plaque-reduction assay with vesicular stomatitis virus in FL cells derived from human amniotic membrane. The patients mainly had Stage III or IV lesion without distant metastasis, and previously had not received any cancer therapy. All of the patients were histologically diagnosed as squamous cell carcinoma. When the serum IFN activity was characterized by acid treatment, significant increases of IFN-alpha/beta/gamma (n = 24, P less than 0.05) and acid-labile IFN (n = 24, P less than 0.001), and significant decrease of acid-stable IFN (n = 24, P less than 0.001) in the cancer patients of 50-to-79-year age group were found, as compared with those in the normal controls of the same age group (n = 20). When IFN titers including various immunologic parameters of the patients and normal controls were simultaneously assayed prior to the beginning of the cancer therapy, the titers of IFN-alpha/beta/gamma, acid-stable IFN, and acid-labile IFN were significantly correlated with some immunologic parameters such as natural killer (NK) activity, the absolute number of T gamma lymphocytes, the percentages of beta- and gamma-globulin, and the amounts of IgA, IgG, IgM, and beta 2 microglobulin. To define further the nature of this IFN, both sera of the patients and normal donors of 50-to-79-year age group were characterized by a neutralization assay with an antiserum to HuIFN-alpha and HUIFN-beta. The IFN activity left when the testing sera were neutralization with these antisera was expressed as gamma-like IFN. The titers of gamma-like IFN in the sera of patients (n = 24, P less than 0.0001) showed a highly significant increase as compared with the normal controls (n = 20). When the correlation between prognosis of the disease and titers of serum IFN were investigated by measuring gamma-like IFN and acid-stable IFN in the sera of patients, all of nine patients with good prognosis after the cancer treatment showed significant decreased levels of gamma-like IFN (P less than 0.01) and acid-stable IFN (P less than 0.05) as compared with those on the time before cancer therapy. On the other hand, titers of gamma-like IFN in the sera of six patients with recurrent disease showed a significant increase as compared with those on the IFN measurement before cancer therapy (P less than 0.05).(ABSTRACT TRUNCATED AT 400 WORDS)

Effects of intradermal administration of streptococcal preparation OK-432 on interferon and natural killer cell activities in patients with oral cancer.

The streptococcal preparation OK-432 was used by intradermal administration as an immunotherapy in 18 patients with oral cancer, and the sera from patients during OK-432 treatment were serially assayed for interferon (IFN) activity by the plaque-reduction method with vesicular stomatitis virus in FL cells derived from human amniotic membrane. The type of serum IFN was characterized by acid-treatment and neutralization test with anti-IFN-alpha and anti-IFN-beta antisera. IFN-gamma was expressed for its titer as the residual IFN activity after neutralization with both antisera. An intradermal injection of OK-432 transiently induced IFN activity and 3 patterns in the type and level of the produced IFN were observed. Although most of the patients induced IFN-gamma and acid-stable IFN or only IFN-gamma, 2 patients seemed to be unresponsive to OK-432. When we examined the relationship between natural killer (NK) activity and IFN titer, a sharply declined NK activity was found immediately post OK-432 administration, and then NK activity stayed around the pretreatment level. Most of the tested patients' induced IFN-gamma, preceding the step toward the gradual increase in NK activity, decreased with OK-432. However, even in the patients showing no IFN induction with OK-432, a significant decrease of NK activity occurred.

Effects of 5-fluorouracil and the combination of 5-fluorouracil and human leukocyte interferon on human salivary gland adenocarcinoma cell line in culture.

The growth inhibitory effects of 5-fluorouracil (5-Fu) and the combination of 5-Fu and human leukocyte interferon (HuIFN-alpha) on the human salivary gland adenocarcinoma cell line HSG in culture were examined by measuring colony formation in the semi-solid agar medium and cell proliferation in the monolayer culture. As a consequence, the colony-forming ability of HSG cells in the agar medium containing 5-Fu was found to be markedly inhibited as compared with the untreated control. The concentration of 5-Fu yielding 50% inhibition of colony-forming ability of HSG cells under the presence of 5-Fu was 0.08 micrograms/ml. When the growth inhibitory effects of the combination of 5-Fu and HuIFN-alpha on HSG cells were examined, the colony forming ability of HSG cells was synergistically inhibited, whereas effects of the combined treatment on HSG cells in the monolayer culture were less sensitive than those on the colony formation. These findings strongly suggest that the combination of 5-Fu and HuIFN-alpha or 5-Fu alone is selectively effective on the neoplastic cells of HSG cell population but not on the non-neoplastic cells.

In vitro effect of androgen on RNA synthesis in nuclei from androgen-independent subline of Shionogi carcinoma (CS 2).

By serial transplantation of CS 1, a subline of Shionogi carcinoma SC 115, to female mice, another subline was obtained and designated CS2. The subline showed a complete loss of androgen dependency on the growth of the tumor. When male mice bearing the tumor were castrated and treated with testosterone, the activity of RNA polymerase I in isolated nuclei from the tumor hardly varied during the period of the experiments (36 h), while the activity of RNA polymerase II exhibited a transient increase (about 40%) at 6 h after the testosterone injection. The results, together with the previous ones showing 80% and 40% increases in RNA polymerase I activity at 24 h after testosterone administration in the case of SC 115 (androgen-dependent tumor) and CS 1 (less androgen-dependent tumor), respectively, indicate that the stimulation of RNA polymerase I activity by androgen in the tumor tissues is closely related to the androgen dependency on the growth of the tumors.

An odontogenic myxofibroma related to an embedded third molar of the mandible. Report of a case.

A case of odontogenic myxofibroma involving the angle of the mandible is reported. This case arose in the area closely associated with the pericoronal portion of the embedded third molar. When the mandible resected was histopathologically examined, the tumor mass containing various shapes of epithelial cell nests and amorphous calcified bodies in the myxomatous fibrous tissue was found to be formed in the localized area well-demarcated by the enamel of the embedded tooth. These findings strongly suggest that this lesion is of odontogenic origin.

Sensitivity of a neoplastic epithelial duct cell line from a human submandibular salivary gland to human leukocyte interferon as assessed by an in vitro semi-solid agar technique.

A neoplastic epithelial duct cell line from a human submandibular salivary gland, HSG, was assayed by an in vitro semi-solid agar technique for sensitivity to human leukocyte interferon (HuIFN-alpha). The clone which showed the most stable growth and the greatest ability of colony formation in the agar medium, was isolated from the colonies of HSG cells and used in the present study. This clone was designated as HSG-1. As a consequence, cultivation of HSG-1 cells in the agar medium containing HuIFN-alpha of 1000 units/ml resulted in the inhibition of 47.6% of the colony-forming ability of HSG-1 cells, as compared with the untreated control. Addition of increasing concentrations of HuIFN-alpha (between 100 units/ml and 1000 units/ml) in the agar medium caused a linear reduction in the number of the colonies, ranging from 5.2% to 47.6%. Moreover, addition of HuIFN-alpha showed an inhibitory effect on the multiplication of HSG-1 cells in the monolayer culture. These observations strongly suggest that HuIFN-alpha has antineoplastic and antiproliferative effects on HSG-1 cells.

Interaction of adenosine and acetylcholine on the bullfrog atrium.

As adenosine has a potent stabilizing action on catecholamine stimulation in the myocardium, the mode of interaction of adenosine and acetylcholine (ACh) was studied with regard to the membrane potential, current and tension components of the bullfrog atrium, using the single or double-sucrose gap method. Adenosine (10(-4)-3 x 10(-3)M) augmented the twitch contraction in the presence of ACh(10(-9)-5 x 10(-7)M) by lengthening the duration of the action potential. The dose-tension response curve for ACh was modified by adenosine, producing a rise of the inhibitory threshold of ACh, and the modification showed a non-competitive interaction of these compounds. Under the voltage clamp, ACh-induced steady current (IACh) was inhibited by adenosine non-competitively. The known inhibition of slow inward current (Is) by ACh was enhanced by adenosine, while the delayed outward current (Ix) was markedly suppressed. Is-dependent and -independent tension components were both inhibited by adenosine, thereby suggesting a decrease in intracellular concentrations of calcium. The potent suppression of IACh and Ix induced by adenosine, however, appeared to mitigate the inhibitory action of ACh on the action potential and twitch contraction.