High-dose nebulized budesonide is effective for mild asthma exacerbations in children under 3 years of age.

Background. High-dose inhaled steroid therapy has been shown to be effective in children and adults with asthma exacerbations. However, few reports are available regarding its efficacy for asthma exacerbations in younger children. Objective. In this study, we administered high-dose nebulized budesonide therapy for mild asthma exacerbations in children < 3 years of age and compared its efficacy and safety with systemic steroid therapy. Methods. This study included children < 3 years old with mild asthma exacerbations. Patients were randomly assigned to two groups: the BIS group was given 1 mg of nebulized budesonide twice daily, and the PSL group received prednisolone 0.5 mg/kg iv three times daily. Days to disappearance of wheezing, days of steroid use, days of oxygen use, serum cortisol level, and incidence of adverse events during treatment were compared between the groups. Result. Wheezing disappeared after an average of five days, and steroids were administered for an average of five days in both groups, with no significant difference in days of oxygen use. Serum cortisol levels at initiation and during the course of treatment remained unchanged in the BIS group, and were decreased in the PSL group; however, the decrease in the latter group was not pathologic. Conclusion. For children < 3 years old with mild asthma exacerbations, high-dose nebulized budesonide therapy is equally as effective as systemic steroid therapy.

Salivary gland scintigraphy in gastro-esophageal reflux disease.

UNLABELLED: Gastro-esophageal reflux disease (GERD) is associated with a decreased salivary flow as well as gastric acid production. This study therefore aimed to investigate functional disorders of salivary glands in patients with GERD. METHODS: Thirty-one consecutive patients with GERD underwent salivary gland scintigraphy. RESULTS: If the results defined the optimal cutoff point for determining the decreased salivary secretion as 51 % in parotid glands and 36 % in submandibular glands, a decreased salivary secretion of right parotid gland, left parotid gland, right submandibular gland, and left submandibular gland was found in 39 %, 32 %, 36 %, and 58 %, respectively. Overall, salivary function disorder of at least one major salivary gland was found in 24 patients (78 %) with GERD. There was no difference in the incidence of impaired salivary function between GERD patients with and without erosive esophagitis. Salivary gland function was more frequently diminished than expected in GERD. We concluded that the presence of impaired salivary gland function was considered to be one of risk factors for developing GERD symptoms.

Inhalation of nebulized nitroglycerin in dogs with experimental pulmonary hypertension induced by U46619.

BACKGROUND: Pulmonary hypertension (PH) causes mortality in some congenital and acquired heart and lung diseases. However, inhalation of NO gas requires complicated and expensive instruments and elaborate preparations to avoid toxic gas administration. We tested the effectiveness and safety of inhaled nebulized nitroglycerin (Neb-NTG) in dogs with experimental PH. METHODS: Experimental PH was induced by continuous infusion of a thromboxane analog (U46619). The U46619 infusion rate was adjusted to maintain a systolic pulmonary artery pressure (PAP) at 40 mmHg in 10 anesthetized and mechanically ventilated dogs. Then, 20 micrograms/kg of NTG liquid nebulized by compressed air was inhaled. RESULTS: After infusion of U46619, the systolic, diastolic and mean PAP increased by 119%, 228% and 169%, respectively, and the systolic, diastolic and mean systemic arterial pressures (SAP) increased by 19%, 29% and 23%, respectively. The systolic pulmonary to systemic pressure ratio (Pp/Ps) and mean Pp/Ps increased by 83% and 113%, respectively, and the pulmonary vascular resistance (PVR), systemic vascular resistance (SVR) and pulmonary to systemic resistance ratio (Rp/Rs) increased by 341%, 100% and 145%, respectively. After inhalation of Neb-NTG in dogs with experimental PH, systolic, diastolic and mean PAP and PVR decreased by 25 +/- 4, 26 +/- 11, 25 +/- 9 and 31 +/- 21%, respectively. There were no significant changes in systolic, diastolic and mean SAP, SVR, cardiac output and plasma methemoglobin concentrations. The systolic and mean Pp/Ps decreased by 18 +/- 7 and 20 +/- 7%, respectively. The Rp/Rs decreased by 25 +/- 13%. CONCLUSIONS: The results of this study demonstrate that Neb-NTG is an effective and selective pulmonary vasodilator and may offer a new therapeutic option for PH.

Successful interstitial treatment for bilateral tongue cancer.

We report three cases of bilateral tongue cancer who received interstitial brachytherapy successively for each tumour. Tumour control following treatment are as good as that for unilateral tongue cancer and there have been no severe complications in, or around, the tumour area after using a mandibular protective spacer and dose reduction for the second treatment.

Factors affecting mandibular complications in low dose rate brachytherapy for oral tongue carcinoma with special reference to spacer.

PURPOSE: To evaluate the efficacy of a spacer in the prevention of mandibular complications in low dose rate (LDR) brachytherapy (BRT) for oral tongue carcinoma. METHODS AND MATERIALS: A retrospective analysis was conducted using 103 patients with T1 or T2 tongue carcinoma treated by a single plane implantation of iridium (192Ir) pins between 1979-1994. Of these patients, 60 were treated by BRT alone, and the rest were combined with external irradiation (Ext) and/or chemotherapy (CHT). Forty-eight and 55 patients were given BRT with and without a spacer, respectively. Spacers were individually made of acrylic resin according to a prosthetic technique so as to obtain the thickness of 7-10 mm at the lingual part of the implanted side. Variables, including a spacer, which may be associated with the development of osteoradionecrosis (ORN) of the mandible, were analyzed by the Cox proportional hazards regression analysis. RESULTS: Our spacer reduced about 50% of the absorbed dose at the lingual side surface of the lower gingiva (LSG) to that in the absence of a spacer. Absolute incidence of ORN was 2.1% (1 of 48) and 40.0% (22 of 55), with and without a spacer, respectively, and the difference was statistically significant by univariate analysis (p = 0.0004). It was revealed by the Cox analysis that the spacer (p = 0.0247), combined CHT (p = 0.0295), and combined Ext (p = 0.0279) were significant independent factors associated with the development of ORN. The spacer was shown to be a significant factor by univariate analysis (p = 0.0037), but not by multivariate analysis when analysis was restricted to the patients who did not receive CHT. The absorbed dose, dose rate, and biological effective dose (BED) reflecting early or late response were estimated at the LSG, and prognosticators associated with the incidence of ORN were also determined by the Cox analysis. Particularly, BED for late response by BRT, the total absorbed dose, and any BED by Ext plus BRT were highly significant factors in the whole population. Essentially similar results were obtained in the patients without receiving CHT. CONCLUSIONS: It was clarified that our spacer effectively prevents mandibular complications in LDR BRT by 192Ir for oral tongue carcinoma. Furthermore, introduction of a spacer provided novel information concerning the development of ORN, where BED particularly for late response given by BRT, the total absorbed dose, and any BED by Ext plus BRT could be good prognostic factors only when estimated at the LSG.

External and interstitial radiotherapy in the treatment of oropharyngeal squamous cell carcinoma.

The records of 165 patients with squamous cell carcinoma of the oropharynx treated at our hospital with external and/or interstitial radiotherapy between 1971 and 1990 were reviewed to evaluate the treatment results, focusing on primary control and complications. All cancers were restaged according to the UICC 1987 TNM staging system. Of these 165 patients, 11% were in Stage I, 55% in Stage II, 24% in Stage III and 8.5% in Stage IV. Local control and complications were analysed in 140 patients. The remaining 25 patients died of intercurrent or metastatic disease during the first 2 years following treatment and were excluded from the analysis. 70 patients were treated by interstitial implant using permanent implant seeds (Rn-222 in eight patients, Au-198 in 62 patients) with or without external radiation. 56 other patients received external irradiation alone and another 14 patients received pre-operative external irradiation plus surgery. 2-year recurrence-free rates were 73% (100% for T1, 76% for T2, 36% for T3 tumours) in the patients who received interstitial implant with or without external radiation and 36% (67% for T1, 48% for T2, 13% for T3 tumours) in the patients treated by external irradiation alone. The incidence of soft-tissue or bone complications requiring long-term treatment was 14%. Based on these findings, it is believed that an interstitial implant using Au-198 grains combined with external beam irradiation is a useful treatment modality for small lesions of the oropharynx.

Squamous cell carcinoma of the maxillary sinus and the oral part of the upper jaw. Comparison of treatment results.

The treatment results were compared in 77 patients with maxillary sinus squamous cell carcinoma (MC) and 53 patients with squamous cell carcinoma arising from the oral part of the upper jaw (OC). Both sets of patients received radiotherapy alone, or radiotherapy combined with surgery and/or chemotherapy. Computerized tomography was useful for the definition of the treatment volume. Intraarterial chemotherapy was given in 89 of 130 patients and in these patients the total radiation dose was reduced by about 10 Gy. No difference was found in the 5-year survival rate between the MC (65%) and the OC (66%) groups. The cumulative incidence of local failure was higher in MC (36%) than in OC (26%), whereas the ultimate incidence of neck node metastasis was higher in OC (43%) than in MC patients (18%). Half of the inoperable patients (9/18) were older than 80 years and had contraindications to anaesthesia and major surgery. The local recurrence rate was high in the inoperable MC patients (6/8). Contralateral sinus cancers occurred in 4 patients in the MC group.

Brachytherapy for stage I & II oral tongue cancer: an analysis of past cases focusing on control and complications.

An analysis of the therapy used for 370 tongue cancer patients has been made, said patients having been treated by interstitial irradiation alone or by combined external irradiation and brachytherapy (Stage I:90 cases, IIa: 196 cases; and IIb: 84 cases). The neck was followed by close follow-up (304 cases), treated by elective neck irradiation (56 cases), or underwent operation at the time of local recurrence (10 cases). The results have shown that the 5-year survivals for Stages I, IIa, and IIb were 84%, 78%, and 72%, respectively. further, the 5-year primary control was 85% for tumors of the superficial type, 79% for tumors of the exophytic type, and 45% for tumors of the infiltrative type (p < 0.004). In non-electively irradiated patients, a neck metastasis occurred in 31% in Stage I, 41% in Stage IIa, and 51% in Stage IIb. Finally, 110 patients incurred radiation-induced complications (110/291 = 38%) and 11 patients (11/291 = 4%) required a surgical procedure. Brachytherapy for tongue cancer achieved results that are comparable with surgery. The analysis also revealed that the introduction of computer dosimetry and the use of a spacer (a dental guard) in brachytherapy have achieved superior results in the management of a tongue cancer.

Brachytherapy for non-metastatic squamous cell carcinoma of the buccal mucosa. An analysis of forty-five cases treated with permanent implants.

An analysis has been undertaken of 45 patients with non-metastatic squamous cell carcinoma of the buccal mucosa treated by permanent 198Au or 222Rn implants and in most cases supplementary external irradiation. Eight patients had T1, 30 had T2, and 7 T3 disease. Of the lesions 21 were located in the buccal mucosal surface, 14 in the retromolar region, and 10 in the bucco-alveolar sulci. Seven of the 45 (16%) died of the disease and the actuarial 5-year survival rate was 81%. No obvious differences were noted in survival rate between different stages of the disease or between different subsites of the primary lesion. There were 6 local recurrences occurring from 3 to 33 months after treatment, and only one of these was salvageable by further radiation therapy. Neck node metastasis occurred in 11 cases from 2 to 34 months after treatment, and 8 of these cases responded successfully to a radical neck dissection or radiotherapy.

The efficacy of radiation therapy for a malignant melanoma in the mucosa of the upper jaw: an analytic study.

An analysis has been made of the effect of radiation therapy in 28 patients with a malignant melanoma (Stage I: 18 cases; Stage II: 10 cases) in the mucosa of the upper jaw. Treatment had been provided by one of the following methods: intraoral mold (10 cases), interstitial brachytherapy (two cases), intraoral electron therapy (nine cases), or external irradiation (seven cases). The results have shown that the survival rate for all 28 patients was 25%, and that the survival rate for stage I patients treated by intraoral electron or brachytherapy was 47%. The primary tumor control rate in percentages was 79% (22/28) in all 28 radiotherapy patients; 92% (11/12) for tumors treated by a mold or an interstitial implant; 67% (6/9) for tumors treated by an intraoral cone; and 71% (5/7) for tumors treated by external irradiation with or without surgery. A neck metastasis that was found in 19 patients was treated by surgery, radiotherapy, and/or immunochemotherapy, and the result was successful in nine patients. The major factor in the failure of treatment was a distant, metastatic dissemination. This analysis revealed that radiotherapy has achieved similar or better results than surgery and may be advocated for the management of a localized malignant melanoma in the mucosa of the upper jaw.

Causes of oral tongue cancer treatment failures. Analysis of autopsy cases.

Eighty-three autopsy cases of squamous cell carcinoma of the oral tongue were reviewed to identify retrospectively the causes of treatment failure. The cure rate for the primary cancers at autopsy was 48.2% (40 of 83). Regional lymph node metastases were found in 71.1% (59 of 83). Regional metastases and/or juxtaprimary recurrence frequently spread continuously and diffusely, forming bulky neck tumors in 38.6% (32 of 83). The incidence of distant lymph node metastasis (below the clavicle) and hematogenous metastasis was 35.4% (29 of 82) and 58.5% (48 of 82), respectively. The lung was the most common site of hematogenous metastases (52.4%, 43 of 82). Hematogenous metastasis occurred more frequently in the younger age group (less than 40 years of age; P = 0.03). Distant lymph node metastases were identified in the lung hilar, bifurcation, and paratracheal nodes in 89.7% (26 of 29) and had a statistically significant association with lung hematogenous metastasis. Univariate analysis revealed that gross appearance, tumor stage, clinical stage, presence of cervical lymph node metastasis, and interval from N0 to NX were significant predictors of survival time (duration from initial treatment to death). Rupture of the neck vessels was fatal in eight patients (9.6%), and hypercalcemia was seen in six (7.2%). Pulmonary infection was the direct cause of death in 33.7% of patients (28 of 83). Secondary malignant lesions occurred in 22.9% (19 of 83).

Usefulness of 198Au grain implants in the treatment of oral and oropharyngeal cancer.

A series of 177 patients with squamous cell carcinoma of the oral cavity and oropharynx were treated with 198Au grain (gold grain) implants. Sites of the lesion included the tongue, mouth floor, buccal mucosa and oropharynx, especially the soft palate and faucial arch. Three-fourths of the patients were treated in combination with prior external beam irradiation. A permanent implant dose (total decay) of 80-90 Gy was given in the form of gold grains alone and in combination with an external dose of no more than 30 Gy, and 60-70 Gy, total decay, was given after an external dose greater than 30 Gy. The 2-year recurrence-free rate was 86.2% in the case of T1N0, 72.6% in T2N0 and 72.2% in T3N0. The difference in the results of implant therapy alone and combined therapy was not significant. Late complications were minimal after grain implantation alone, and when used in combination, less than 70 mCi of grain activity after a 40 Gy external dose did not seem to be a serious hazard with respect to bone damage except in the case of cancer of the mouth floor. Gold grain implants were useful and easily applied under local anesthesia to early or superficial lesions at sites where a rigid linear source could not be used. Exposure of the radiology staff was only 5-10 mrad in the case of the usual 10-15 (50-75 mCi) implant grains.

Chromosome aberration frequencies produced by a 70-MeV proton beam.

The effectiveness of a 70-MeV proton beam in the induction of chromosome aberrations was studied. We employed peripheral lymphocytes and analyzed the frequencies of dicentrics and rings after irradiation at doses ranging from 0.1 to 8.0 Gy at various depths within a Lucite phantom. The frequency of chromosome aberrations after irradiation with an unmodulated proton beam at 5 mm showed a dose-response relationship similar to that of 60Co gamma rays. However, irradiation at greater depths with the spread-out Bragg peak induced higher aberration frequencies at doses lower than those with gamma rays. Furthermore, the distribution curve of chromosome aberration frequencies as a function of depth was found to be slightly different from the physically measured depth-dose curve. With the spread-out Bragg peak the biological effects were more marked at greater depths, resulting in a distribution of relative biological effectiveness values. The results obtained from chromosome aberration analysis may not be related directly to those for the relationship between dose and cell killing. Slight differences in values for relative biological effectiveness due to the change of dose and site of proton beam irradiation may not be important for practical proton beam therapy, but may be important in the prevention of late radiation injuries.

Prognostic factors in head and neck non-Hodgkin's lymphoma with special reference to serum lactic dehydrogenase and serum copper.

An analysis of prognostic variables was performed in a retrospective study of 121 patients with Ann Arbor stage I-II head and neck non-Hodgkin's lymphoma admitted from 1973 to 1988. The overall actuarial 5-year survival rate was 58.8% and the minimum follow-up 15 months. Nine clinical and laboratory parameters were studied, including serum lactic dehydrogenase (LDH) and serum copper (SCL), and subjected to univariate and multivariate analyses. In univariate analysis, histology and LDH were found to be significant prognostic variables. Evaluation by Cox's multivariate proportional hazard model revealed histology, SCL and sex to be of prognostic significance.

Lectin binding in tissues from hydatidiform mole, invasive mole and choriocarcinoma to concanavalin-A, wheat germ agglutinin and peanut agglutinin.

A light microscopic analysis of lectin receptors in normal placenta and trophoblastic disease was performed utilizing biotinylated Concanavalin-A (Con-A), wheat germ agglutinin (WGA), and peanut agglutinin (PNA), in conjunction with an avidin-biotin peroxidase complex. Hydatidiform mole, invasive mole and choriocarcinoma exhibited increased receptors to Con-A and WGA compared to normal placenta. Increased reactivity to Con-A and WGA was associated merely with increased growth and proliferation of trophoblasts rather than a malignant transformation. Normal placenta, partial and complete mole generally showed moderate to strong binding with PNA after neuraminidase treatment, while invasive mole and choriocarcinoma (11 of 15 cases) generally showed minimal to absent reaction with PNA. Heterogeneity of PNA binding in choriocarcinoma was manifested by the presence of PNA reactivity in the trophoblast membrane in 2 cases wherein no prior neuraminidase treatment was given. This suggests that in some malignant trophoblasts, there is absence of sialic acid in the terminal cell surface carbohydrate groups resulting in the exposure of N-acetylgalactoseamine.

Discriminant analysis on the treatment results of interstitial radium tongue implants.

Discriminant analysis was carried out for 48 tongue cancer patients who were treated with radium single-plane implantation. The 48 patients were grouped into 32 successfully cured without complications, five successfully cured with complications, six successfully cured but requiring additional boost therapy and five with local recurrence. To evaluate the relation between the dose distribution and the local treatment results, the analysis was based on a volume-dose relationship. The functions introduced by this discriminant analysis were linear, and the parameters used were modal dose, average dose and shape factors of histograms. Each group of treatment results had a correction rate of greater than 80%, except for the successfully cured group with ulcers. The discriminant functions were useful as an index to obtain a final clinical treatment result at the early time of implantation, and these functions could be used as a criterion for the optimal treatment of tongue carcinoma. We were also able to recognize the limitation of the actual arrangement of sources in the single-plane implant.

[A study on the role of DNA methylation within hCG and hPL genes in trophoblastic disease].

It has been shown that the extent of methylation of cytocine in DNA is inversely correlated with gene expression in many cases. The DNAs extracted from placental tissue, hydatidiform mole and choriocarcinoma tissue were examined to see whether the extent of cytocine methylation is correlated to the gene expression of placental peptide hormones and the transformation of trophoblast. First of all we measured the amount of methylated cytocine per total DNA with HPLC. We then examined cytocine methylation in hCG alpha,beta and hPL genes using methylation sensitive (Hha I, Hpa II) and non sensitive (Msp I) restriction enzymes and molecular hybridization. During pregnancy the total amount of methylated cytocine measured with HPLC increases gradually from 0.72 mol.% at first trimester to 0.92 mol.% at term. The DNA of WBC showed a higher level of methylated cytocine than placental DNA. The extent of DNA methylation in the peptide hormone genes increases during placental development. Hypomethylation in the hCG alpha gene was also seen in molar tissue which expresses a high amount of hCG. Therefore it is inversely correlated that gene expression of hCG alpha,beta and the extent of DNA cytocine methylation. Furthermore some restriction polymorphisms were observed with Msp I in hCG alpha and hPL genes which might be related to malignant transformation of the trophoblast.

[Selective augmentation of cellular hCG alpha mRNA levels and immunoreactive hCG alpha secretion by 17 beta-estradiol in the normal placenta].

In order to elucidate a possible self-regulation for hCG synthesis in placenta, effects of estradiol on hCG production and secretion were evaluated by culturing early placental tissue in the presence or absence of estradiol. The cellular level of mRNAs encoding hCG (alpha, beta) and hPL were estimated by mean grain count per syncytial nucleus on the placental sections hybridized in situ with labeled cDNA probes corresponding to these mRNAs. Immunoreactive hCG, hCG alpha and hPL in the media and explanted tissues were measured by the homologous RIAs. Addition of estradiol at concentration of 1 approximately 10 ng/ml into the medium caused an increase in the cellular levels of hCG alpha mRNA after 24-hour cultured, and exhibited significant increases in immunoreactive hCG alpha levels in the media and explanted tissues after 72-hour culture. The addition of estradiol neither affected the cellular levels of mRNA encoding hCG beta and hPL nor immunoreactive hCG and hPL levels in the media and tissues. The appropriated concentration of estradiol (1 approximately 10 ng/ml) used in above experiments was found to be similar to the tissue concentration in normal placenta. These findings suggest that the physiological concentration of estradiol selectively stimulates hCG alpha synthesis and secretion by normal placenta. Thus, estradiol in placenta may be a factor responsible for the increase of hCG alpha in maternal serum and placental tissue with the progress of gestation.