The clinical efficacy of erythromycin (EM) therapy has been demonstrated in otitis media with effusion (OME). However, the mechanism of action of this drug is not clear. In this study, to elucidate the possible mechanism of action of EM, we examined the effect of the drug on the expression of neutrophil adhesion molecules such as L-selectin and Mac-1. Furthermore, we examined production of leukotrienes B4, C4 (LTB4, C4) and prostaglandin E2 (PGE2) in rat OME induced by injection of a lipopolysaccharide. EM down-regulated L-selectin expression, and inhibited up regulation of Mac-1 expression on peripheral blood neutrophils. Also it inhibited the accumulation of inflammatory cells such as neutrophils and macrophages in middle ear effusion (MEE). Furthermore, EM suppressed the exudation of plasma protein and the production of LTB4, C4 and PGE2, in OME. These results suggest that EM may exert the antiinflammatory effect on MEE through suppression of leukocyte accumulation the middle ear by affecting the expression of adhesion molecules on leukocytes and inhibiting the production of arachidonic acid metabolitis.

Animals↗

PubMed1996

Reactive arthritis induced by tonsillitis.

We describe 13 adult patients with reactive arthritis induced by tonsillitis. Arthritis occurred 710 days after tonsillitis and involved the wrists, knees, feet and sternoclavicular joints. Some cases had pain in the Achilles tendon areas. Synovial fluid examined in 4 patients was sterile. All patients except 3 showed unequivocal elevation of serum ASO and/or ASK. Streptococcus was isolated from tonsillar swabs in 7 patients. One had maculopapular erythema and 2 had abdominal pain of unknown origin, but none had cardiac involvement, chorea and subcutaneous nodule. HLA examination revealed that 4 had B39 (p <0.005). Eight cases were treated with antibiotics. Five cases underwent tonsillectomy. All tonsils had cryptic abscess. No exacerbation was seen thereafter. These cases probably represent reactive arthritis induced by tonsillitis and should be distinguished from other rheumatic diseases.

Adult↗

PubMed1995

Induction chemotherapy with cisplatin, etoposide, and mitomycin-C (PEM) regimen in advanced cases with cancer of pharynx and oral cavity.

With the aim of improving survival rate in advanced head and neck cancer, we scheduled 26 patients to receive PEM regimen. This regimen consisted of cisplatin (CDDP)(P), etoposide (VP-16)(E), and mitomycin-C (MMC)(M) (CDDP 60 mg/ m2/2 hr infusion on day 1; VP-16 40 mg/m2/1 hr infusion on days 1-3; MMC 7 mg/m2 iv bolus on day 1). Of 25 patients evaluable for response, 8 complete response (CR), 14 partial response (PR) were achieved, with an overall response rate (RR) of 88%. Myelosuppression was major side effect and thrombocytopenia (23% greater than WHO grade) was dose limiting toxicity. Other adverse reactions including mucositis were all mild and transient. Since limited mucosal toxicity, full course of following treatment including radiotherapy and/or surgery could be done satisfactorily. We concluded that this regimen produced beneficial effect as the adjuvant setting in patients with cancer in pharynx and oral cavity because of limited mucosal toxicity.

Adult↗

PubMed1995

[Evaluation of arachidonic acid metabolites in experimental rat otitis media with effusion].

Leukotrienes B4, C4 (LTB4, LTC4) and prostaglandin E2 (PGE2) are arachidonic acid metabolites which are released from various types of cells, and are considered to be the mediators of inflammation because of their potent vascular permeability increasing activity (LTC4 and PGE2) and chemotactic activity (LTB4). In this study, to evaluate the involvement of arachidonic acid metabolites in otitis media with effusion, we measured the LTB4, LTC4 and PGE2 in rat middle ear effusion (MEE) by radioimmunoassay (RIA). SD rats weighing about 200g were used. The animals were divided into two groups, and lipopolysaccaride (LPS) or concanavalin A (ConA) was injected into the right middle ear cavity through the tympanic membrane. The left middle ear cavities were injected with 200 microliters of phosphate balanced buffered saline (PBS) and used as controls. After stimulation, middle ear effusion and accumulation of inflammatory cells such as neutrophils, macrophages, and lymphocytes was observed in the middle ear cavity. In contrast, no inflammatory cells were observed in the control ears. Proteins exudated into the middle ear cavity after LPS or ConA injection. The protein content increased up to 3 days, and then decreased. Substantial amounts of LTs and PG were detected in experimental rat OME, although hardly and LTs or PG was detected in the control ears or serum. LTs levels increased up to 7 days, and then decreased. PGE2 levels increased up to 3 days, and decreased thereafter. Dexamethasone effectively suppressed protein exudation, cell accumulation and production of arachidonic acid metabolites in the middle ear.

Animals↗

PubMed1995

Salvage chemotherapy with PEM and long-CF regimen in CDDP refractory advanced head and neck cancer.

With the aim of increasing complete response rates and improving survival in cisplatin (CDDP)-based combinations (CDDP + 5-fluorouracil (5FU) and/or CDDP+methotrexate (MTX)+bleomycin (BLM) of refractory advanced head and neck cancer, we scheduled 21 patients to receive PEM and Long CF, PEM regimens consisting of CDDP (P) Etoposide (Etop) (E) and mitomycin-C (MMC) (M) (CDDP 60 mg/m2/2 hr. infusion on day 1; Etop 40 mg/m2/1 hr. infusion on day 1, 2, 3; MMC 7 mg/m2 iv bolus on day 1). Of 12 patients evaluable for response, 2 CR, 3 PR were realized, with an overall response rate of 42%. Myelosuppression was the major side effect, and thrombocytopenia (8% greater than WHO grade III) was the dose-limiting toxicity. Long CF consisted of CDDP (C) and 5FU (F) (CDDP 8 mg/m2/2 hr. infusion on day 1-5, 8-12, 15-19, 22-26; 5FU 300 mg/m2/24 hr. infusion or tegaful.uracil (UFT-E) 400 mg/m2 P.O. on day 1-28. Of 8 patients evaluable for response, 3 PR were realized, with an overall response rate of 38%. N&V and leukopenia were the major side effects. These adverse reactions were all transient. We concluded that these two regimens produced beneficial effects in patients with advanced recurrent head and neck cancer which had already been treated with CDDP-based combinations.

Aged↗

PubMed1995

A case with quadruple primary cancers of head and neck.

Despite progress in techniques for early detection and treatment of cancers, cases of multiple primary cancers are apparently increasing. This paper reported quadruple primary cancers of stomach, lung, hypopharynx and maxillary sinus in a 63-year-old male. He finally died of brain metastasis and pneumonia by MRSA (Me Resistant S. aureus).

Adenocarcinoma↗

PubMed1993

Synergistic interaction of natural human tumor necrosis factor-alpha/natural human interferon-alpha mixture alone and in combination with cisplatin against head and neck laryngeal squamous carcinoma multicellular tumor spheroids.

We evaluated the effects of each component, natural human tumor necrosis factor-alpha (nHuTNF-alpha) and natural human interferon-alpha (nHu-IFN-alpha), and the combined nHuTNF-alpha/nHuIFN-alpha preparation with or without cisplatin (DDP) at tumor mass level. Multicellular tumor spheroids (MTS) of approximately 500 microns in diameter were produced from HEp-2 laryngeal squamous carcinoma cell line by liquid overlay culture technique. Cell kill effects of 72 hr exposure to nHuTNF-alpha, nHuIFN-alpha, or nHuTNF-alpha/nHuIFN-alpha against cells in MTS were 2-3-fold less than those in monolayer. In MTS, does response curves become progressively flat at high drug concentrations, indicative of poor drug penetration into the MTS core. Combination nHuTNF-alpha/nHuIFN-alpha produced synergistic cell kill for both MTS and monolayers. For monolayer cells exposure to nHuTNF-alpha/nHuIFN-alpha first (72 hr) followed by DDP (1 hr) after 1 hr rest period was synergistic with combination index (CI) of approximately 0.8 at LD50. Simultaneous (72 hr in nHuTNF-alpha/nHuIFN-alpha with DDP in last 1 hr) or reverse order of exposure were antagonistic. In contrast, for MTS, DDP followed by nHuTNF-alpha/nHuIFN-alpha was most synergistic with CI of approximately 0.2. Simultaneous exposure or nHuTNF-alpha/nHuIFN-alpha followed by DDP showed synergism with CI of approximately 0.5 and 0.8, respectively. The improved efficacy of DDP followed by nHuTNF-alpha/nHuIFN-alpha sequence for MTS cells appears to be due to increased nHuTNF-alpha/nHuIFN-alpha penetration into the MTS core aided by DDP.

Carcinoma, Squamous Cell↗

PubMed1993

[Magnetic stimulation of the facial nerve].

Intracranial activation of the facial nerve and the face-associated motor cortex are now possible with noninvasive magnetic stimulation techniques. Compound muscle action potentials (CMAPs) and the Blink reflex, in response to magnetic stimulation, were investigated. Subjects were 10 normal controls and 2 Bell's palsy patients. CMAPs were elicited in the orbicularis oris muscle by magnetic stimulation at the parieto-occipital skull and stylomastoid foramen. Furthermore, CMAPs were evoked by a magnetic coil oriented over the cortex. CMAP recording was possible with magnetic stimulation and the latencies of CMAPs at the parieto-occipital skull were slightly greater than those at the stylomastoid foramen. In 10 normal subjects, the mean onset latency following transcranial magnetic stimulation of the facial nerve at the parieto-occipital skull was 5.07 msec (SD = 0.40), while transcutaneous latency at the stylomastoid foramen was 2.77msec (SD = 0.539). In the blink reflex, R1 latency was 10.99 msec (SD = 1.27), ipsilateral-R2 latency was 37.46 msec (SD = 2.57), and contralateral-R2 latency was 38.925 msec (SD = 3.20). The blink reflex thus had a configuration similar to that evoked by conventional electrical stimulation. In the patients with Bell's palsy, CMAPs elicited by magnetic stimulation were of low amplitude with normal latency. However, in the blink reflex, only a contralateral R2 response could be recorded, and R1 and ipsilateral-R2 showed no response to stimulation at the affected side. Investigation of patients with Bell's palsy using this technique may therefore prove useful in the evaluation of peripheral facial nerve disorders.

Action Potentials↗

PubMed1992

Effects of folinic acid on 5-fluorouracil induced cell lethality with or without cisplatin against head and neck laryngeal squamous carcinoma multicellular tumor spheroids.

We evaluated the efficacy of folinic acid (Leucovorin, LV) on cell lethality induced by 5-fluorouracil (FU) alone or in combination with cisplatin (DDP) by using the HEp-2 laryngeal squamous carcinoma multicellular tumor spheroids (MTS) system. For LV, non-toxic concentration of 10(-5) M was used. For cells in the monolayer, 6 and 24 h exposure to LV increased FU-induced cell lethality approximately 7- and 2-fold, respectively, whereas LV did not influence the effect of FU for MTS. LV's lack of effect on cells in MTS may be interpreted to mean that LV cannot penetrate the MTS. For the monolayer, simultaneous exposure to 3 drugs, DDP, FU and LV, produced synergistic interaction. However, sequential exposures were marginally synergistic or antagonistic, irrespective of sequence of DDP first or last. In contrast, DDP followed by FU plus LV was most synergistic for MTS. Simultaneous exposure was also synergistic, however, FU plus LV followed by DDP was antagonistic. These results suggest that LV is unable to penetrate into the MTS core to potentiate FU activity. DDP appears to have enhanced LV penetration into the MTS core. The exploration of means to overcome limited penetration of LV appears important for successful treatment of head and neck carcinoma.

Carcinoma, Squamous Cell↗

PubMed1992

[Combination chemotherapy of solid tumor--effects of hyaluronidase on doxorubicin (DXR) penetration into multicellular tumor spheroids (MTS)].

We have studied the effects of hyaluronidase (HYD) on the penetration and cell kill effect of doxorubicin (DXR) using multicellular tumor spheroids (MTS). MTS of approximately 500 microns in diameter were prepared by liquid over lay culture technique from PC-10 lung and HEp-2 laryngeal squamous carcinoma cell lines. Cells in MTS and monolayer were exposed for various durations to HYD, followed by 1 hr, rest interval, and by 1 hr. exposure to DXR. MTS and monolayer cells were then trypsinized to a single cell suspension and subjected to clonogenic assay. For PC-10 MTS, pretreatment with HYD for 24 hr. resulted in approximately 10-fold increases in DXR cell kill effects as compared to DXR alone. HEp-2 MTS were more sensitive to HYD pretreatment. Thus, 1 hr. exposure to HYD produced approximately 4-fold increases in DXR-induced cell lethality. Fluorescent microscopic study revealed that 1hr. exposure of MTS to DXR produced DXR fluorescence only 1-2 outer layer of MTS. When MTS were pretreated with HYD, there was an enhanced penetration of DXR fluorescence into the MTS core. HYD-induced enhancement of DXR penetration and its cell kill effect was dependent on the exposure time and tumor cell origin.

Carcinoma, Squamous Cell↗

PubMed1991

Necrotizing sialometaplasia in the mouth floor secondary to reconstructive surgery for tongue carcinoma.

Necrotizing sialometaplasia is a benign inflammatory process, which histologically can mimic squamous cell carcinoma. A 63-year-old man underwent left hemiglossectomy involving transplantation of a myocutaneous flap for squamous cell carcinoma of the tongue. One month after the operation, necrotizing sialometaplasia occurred in the minor salivary gland tissue of the mouth floor, compressed by the necrotic flap. This case is very unusual because of the occurrence of necrotizing sialometaplasia in the floor of the mouth. The etiology of the lesion was considered to be ischemia secondary to compression by the necrotic myocutaneous flap.

Biopsy↗

PubMed1991

[Dipole tracing method analysis for source of auditory brainstem response (wave V) in two normal hearing subjects].

The location and vector moment of the equivalent current dipoles of ABR (wave V) evoked by unilateral acoustic stimuli were estimated in normal adults with the Dipole Tracing (DT) Method. The ABR's were recorded through 21 electrodes arranged according to the international 10-20 standard. The DT method is based on a realistic head shape with uniform volume conductor and individual differences of the skull were corrected for afterwards. The 3-D dipole locations were plotted on the cross-sectional MRI data of the subject. As a result the dipole of the wave V of auditory brainstem responses was found near the contralateral midbrain.

Acoustic Stimulation↗

PubMed1990

[Induction and functional analysis of gamma delta TCR-bearing T cells from human tonsil by Streptococcus pyogenes stimulation].

The killer cell characteristics of gamma delta TCR-bearing T cells induced from human tonsil by streptococcus pyogenes stimulation were examined. Immunohistologic staining of tonsil showed that gamma delta TCR-bearing T cells were mainly located in the interfollicular area connected with stratified squamous epithelium. Streptococcus pyogenes could induce the proliferation of gamma delta TCR-bearing T cells from tonsil in the presence of low-dose of IL-2. This streptococcus pyogenes-induced gamma delta TCR-bearing T cell proliferation was likely to be independent on the IL-2/IL-2R system since an obvious inhibition was not observed with anti-IL-2 and anti-IL-2R mAbs. More importantly, these gamma delta TCR-bearing T cells exhibited cell-mediated cytotoxic activity in a 4 hr 51 Cr-release assay. In addition, immunocytochemical staining revealed that these cells contained a killer protein perforin. These results demonstrate that gamma delta TCR-bearing T cells from tonsil exhibit typical killer cell characteristics. These data also suggest that gamma delta TCR-bearing T cells in human tonsil may play a cytotoxic role in protecting the integrity of tonsil from infection.

Cytotoxicity, Immunologic↗

PubMed1989

Treatment of laryngotracheoesophageal cleft.

Four patients with laryngotracheoesophageal cleft were treated in our institution. Two of the patients survived and two died. Cleft levels ranged from partial 15 mm laryngotracheoesophageal to total with extended right bronchoesophageal cleft.

Bronchi↗