Total serum IgE level influences oral food challenge tests for IgE-mediated food allergies.

Probability curves predicting oral food challenge test (OFC) results based on specific IgE levels are widely used to prevent serious allergic reactions. Although several confounding factors are known to affect probability curves, the main factors that affect OFC outcomes are currently unclear. We hypothesized that an increased total IgE level would reduce allergic reactivity. Medical records of 337 and 266 patients who underwent OFCs for 3.5 g boiled hen's egg white and 3.1 ml raw cow's milk, respectively, were examined retrospectively. We subdivided the patients into three groups based on total IgE levels and age by percentile (<25th, 25-75th, and >75th percentiles), and logistic regression analyses were performed on each group. Patients with higher total IgE levels were significantly less responsive. In addition, age did not significantly affect the OFC results. Therefore, total IgE levels should be taken into account when predicting OFC results based on food-specific IgE levels.

[Liposarcoma of the pleural cavity; report of a case].

A 43-year-old-woman who had sever anterior chest pain visited our hospital on April 3, 2000. A well-defined abnormal shadow was seen in the middle and lower field of the right lung on chest X-ray. Computed tomography showed a large fat density mass in the right pleural cavity with a septum enhanced by contrast medium. Percutaneous needle biopsy revealed lipoma or liposarcoma. Complete resection could be done with combined resection of right lung, lpericardium, parietal pleura and diaphragm. Final histologic diagnosis was well differentiated liposarcoma. There are few reports of liposarcoma arising in the thoracic cavity, we present our case and review the 23 cases reported from the Japanese literatures.

Human mast cell progenitors in peripheral blood from atopic subjects with high IgE levels.

BACKGROUND: It remains unclear whether the number of circulating mast cell progenitors is increased in patients with atopic diseases. Distinct genotypes are reported to affect mast cell/basophil activation. OBJECTIVE: We compared the number and function of mast cell progenitors present in the peripheral blood from donors with normal IgE (IgE < 400 U/mL) and those with atopic dermatitis accompanied by high serum IgE (IgE > 5000 U/mL). METHODS: Purified peripheral blood cells were cultured in serum-free methylcellulose containing stem cell factor (SCF), IL-6 plus IL-3. Fresh methylcellulose containing the cytokines was layered over every 2 weeks. The cultured mast cells were retrieved from the methylcellulose and were functionally analysed. RESULTS: Mast cell colonies were distinguished at 6 weeks of culture as other colony types had been degenerated. The number of mast cell colony-forming cells varied depending on donors and was not significantly increased in peripheral blood from the hyper-IgE atopic patients. A significant inversed correlation was found between the number of mast cells per one colony and the ages of donors. The cultured mast cells derived from atopic patients and those from normal IgE donors equally expressed Fc epsilon RI and released histamine through Fc epsilon RI, although IL-4 priming in vitro markedly enhanced the function of mast cells regardless of donors. CONCLUSIONS: These results indicate that the number of circulating mast cell progenitors may be regulated by unknown individual factors unrelated to IgE levels. Mast cell function may be regulated largely by environmental factors, such as IL-4, but not determined by their progenitors' genotypes.

Randomized study of dose or schedule modification of granulocyte colony-stimulating factor in platinum-based chemotherapy for elderly patients with lung cancer.

It is generally believed that elderly patients are less able to tolerate aggressive cancer chemotherapy than their younger counterparts. Bone marrow cellularity diminishes with age and elderly patients may have decreased tolerance to myelosuppressive agents. Between November 1995 and October 1999, 68 chemotherapy-naive elderly (70 or more years old) patients with histologically or cytologically proven lung cancer who were to receive platinum-based chemotherapy were enrolled in this study. All patients had adequate cardiac, hematological, liver and renal function to receive chemotherapy. Patients were randomized into 3 groups. Patients in groups 1 and 2 received 2 microg/kg and 4 microg/kg granulocyte colony-stimulating factor (G-CSF, lenograstim), respectively, when grade 3 leukopenia (<2,000/microl) or neutropenia (<1,000/microl) appeared after chemotherapy. Patients in group 3 received 2 microg/kg G-CSF when grade 2 leukopenia (<3,000/microl) or neutropenia (<1,500/microl) appeared after chemotherapy. G-CSF was stopped in all groups when the leukocyte count increased to over 10,000/microl or the neutrophil count exceeded 5,000/microl. Full blood cell counts were examined 3 times a week after chemotherapy. All patients received platinum-based chemotherapy. Eighteen, 16 and 22 patients (78%, 73% and 96%) in groups 1, 2 and 3, respectively, received G-CSF when leukopenia or neutropenia appeared. The durations of G-CSF treatment required by groups 1 and 3 (5.7+/-3.6 and 6.6+/-3.2 days, respectively) did not differ significantly, but the duration of treatment required by group 2 (3.7+/-2.8 days) was significantly shorter than that of group 1 (p=0.048). The duration of grade 4 neutropenia in group 2 (0.7+/-1.1 days) was marginally shorter than that in group 1 (1.6+/-2.1 days, p=0.076). The neutrophil nadir of group 2 (949+/-757/microl) was marginally higher than that of group 1 (592+/-438/microl, p=0.058). No patients in group 2 experienced grade 4 neutropenia for 4 days or more or a neutrophil nadir less than 100/microl a significant difference from group 1, where 22% and 17% of patients experienced these events (p=0.02 and p=0.04, respectively). Similarly, no infections requiring antibiotics after chemotherapy occurred in patients in group 2, a significant difference from group 1 (26%, p=0.01). The rates of neutropenia and infection in groups 1 and 3 did not differ significantly. The peak plasma concentration of G-CSF in group 2 was significantly higher than in group 1 (p=0.0018), but did not differ significantly between groups 1 and 3. Doubling the dose of G-CSF could help to decrease neutropenia and prevent infection after chemotherapy in elderly patients with lung cancer.

Observation of toroidal flow antiparallel to the drift direction in the hot electron mode plasmas in the compact helical system.

A toroidal flow antiparallel to the drift direction is observed in the hot electron mode plasmas when a large positive electric field and a sharp electron temperature gradient are sustained inside the internal transport barrier in the Compact Helical System. This toroidal flow reaches up to 5x10(4) m/s at the plasma center, and it is large enough to reverse the toroidal flow driven by a tangentially injected neutral beam. These observations clearly show the plasma favors flow in the minimum nablaB direction at the transport barrier.

Increased expression levels of p53 correlate with good response to cisplatin-based chemotherapy in non-small cell lung cancer.

In order to determine whether expression of the tumor suppressor gene p53 in non-small cell lung cancer (NSCLC) correlates with chemotherapeutic response, resected tumors from 18 patients with recurrent lung cancer who had undergone complete resection and received chemotherapy after the initial tumor recurrence were subjected to p53 immunostaining. Histological examination of the resected tumors revealed 11 adenocarcinomas, 6 squamous cell carcinomas and one adenosquamous cell carcinoma. Group 1 was 50% (n=9) p53-immunopositive. All patients received cisplatin-based chemotherapy after recurrence. No patient in group 1 achieved response to chemotherapy whereas 2 and 3 in group 2 achieved complete and partial responses, respectively. The chemotherapy response rate of group 2 (56%) was significantly higher than that of group 1 (0%, p=0.009). The times to reoccurrence after tumor resection of group 2 was significantly better than that of group 1 (log-rank p=0.019, Wilcoxon p=0.042), and survival after chemotherapy of group 2 was also significantly better than that of group 1 (log-rank p=0.023, Wilcoxon p=0.034). It is suggested that high p53 expression levels in tumors correlate with both good response to cisplatin-based chemotherapy and good survival of patients with advanced NSCLC.

Prophylactic administration of granulocyte colony-stimulating factor when monocytopenia appears lessens neutropenia caused by chemotherapy for lung cancer.

In a retrospective study, we showed that a monocyte count of <150/microl on days 6 to 8 might be a predictor of grade III or IV neutropenia during cancer chemotherapy given at 3- or 4-week intervals. In the present study, we investigated whether the administration of granulocyte colony-stimulating factor (G-CSF) when monocytopenia appears lessens neutropenia during chemotherapy for lung cancer. Between June 1997 and August 1998, 60 patients who received chemotherapy at 3- or 4-week intervals for unresectable lung cancer were randomized to receive G-CSF (2 microg/kg or 50 microg/m2) when monocytopenia (<150/microl) appeared on days 6 to 8 after chemotherapy (group A) or when neutropenia (<1,000/microl) or leukopenia (<2,000/ microl) appeared after chemotherapy (group B). The administration of G-CSF was stopped when the leukocyte or neutrophil counts reached > 10,000/microl or 5,000/microl, respectively. The blood cells counts were examined three times a week and the degree, duration, and frequency of chemotherapy-induced neutropenia of the two groups were compared. One patient in group A was excluded because whole brain irradiation during chemotherapy was required. Twenty-nine and 30 patients in groups A and B, respectively, received platinum-based chemotherapy and their chemotherapy-induced hematologic toxicities were analyzed. The mean neutrophil count nadir of group A (1,558 +/- 1,771/microl) was significantly higher than that of group B (810 +/- 639/microl, p = 0.032). The duration of grade III neutropenia in group A (1.4 +/- 1.7 days) was significantly shorter than that in group B (2.9 +/- 1.9 days, p = 0.004), and the frequency of grade III neutropenia in group A (48%) was significantly lower than that in group B (83%, p = 0.002). Infectious episodes occurred in five and eight patients in groups A and B, respectively. The durations of G-CSF therapy required by group A and B patients (4.8 +/- 3.1 vs. 4.7 +/- 2.7 days) were not significantly different. Prophylactic administration of G-CSF did not exacerbate anemia or thrombocytopenia induced by chemotherapy. We conclude that the prophylactic administration of G-CSF when monocytopenia appears can lessen neutropenia caused by chemotherapy for lung cancer without increasing the total G-CSF dose.

Increased expression levels of cyclin-dependent kinase inhibitor p27 correlate with good responses to platinum-based chemotherapy in non-small cell lung cancer.

In order to determine whether expression of the cyclin-dependent kinase inhibitor p27 in non-small cell lung cancer (NSCLC) correlates with chemotherapeutic response, resected tumors from 22 patients with recurrent lung cancer who had undergone complete resection and received chemotherapy after the initial tumor recurrence were subjected to p27 immunostaining. Histological examination of the resected tumors revealed 14 adenocarcinomas, 7 squamous cell carcinomas and one adenosquamous cell carcinoma. Fifty percent or less and over 50% of the cells in the resected tumors of 11 patients each (groups 1 and 2, respectively) were p27-immunopositive. All but one patient received platinum-based chemotherapy after recurrence. Only one in group 1 achieved a partial response (PR) in chemotherapy whereas 2 and 4 in group 2 achieved complete and PRs, respectively. The chemotherapy response rate of group 2 (54%) was significantly higher than that of group 1 (9%, p=0.022). The times to recurrence after tumor resection of the 2 groups did not differ significantly (log-rank p=0.23, Wilcoxon p=0. 32), but survival after chemotherapy of group 2 was significantly better than that of group 1 (log-rank p=0.045, Wilcoxon p=0.028). It is suggested that high p27 expression levels in tumors may predict the good responses to platinum-based chemotherapy for NSCLC.

Reduction of tablet coloration at tableting for oily medicine (tocopheryl nicotinate).

The powder (TN-PO) which adsorbed D,L-tocopheryl nicotinate (TN) as an oily medicine was prepared using porous calcium silicate (Florite(R)RE, FLR) as an adsorbing carrier. Tablets (TN-TAB) were produced by compression of TN-PO at different compression pressures. As TN-PO was compressed at the higher TN content in TN-PO and compression pressure, the more TN was exuded from TN-PO, and an increase in the degree of tablet coloration was observed. Therefore, FLR or colloidal silica (AEROSIL(R)200, AER) was newly added to TN-PO at compression to reduce the degree of tablet coloration. Further, the effects of addition of FLR or AER on the crushing strength, friability, porosity and disintegration property of the tablet and the dissolution property of TN from the tablet were studied. After addition of FLR or AER, a similar reduction of tablet coloration was observed. When the addition percentage of FLR to TN-PO exceeded 30%, the crushing strength of the tablet increased significantly. On the other hand, when TN-PO added with AER was compressed, no change was observed in the crushing strength of the tablet. The disintegration time of the tablet with added FLR was shorter than that of the tablet with added AER. At every addition percentage studied, the tablet with added FLR showed a higher releasing ability of TN compared with the tablet with added AER. These results indicate that it is possible to reduce tablet coloration by adding FLR or AER at compression of TN-PO. Further, it is considered that the differences in the crushing strength, disintegration property and dissolution property of TN between the tablets with added FLR or AER resulted in different liquid adsorbing and holding mechanisms of FLR particles and AER particles.

Evaluation of the staphylococcal exotoxins and their specific IgE in childhood atopic dermatitis.

BACKGROUND: Superantigenic exotoxins produced by Staphylococcus aureus and their specific IgE antibodies are thought to be important precipitating factors of atopic dermatitis (AD), but there are few reports evaluating these 2 factors at the same time. OBJECTIVE: We examined whether the presence of the exotoxins sampled from the skin of patients with AD and the levels of anti-exotoxin IgE antibodies in their sera correlated with their severity of AD. METHODS: Patients with mild-to-severe AD, 1 to 22 years of age, were evaluated by using Leicester's scoring system. Specific IgE antibodies against these exotoxins were determined by using ELISA. S aureus was isolated from 3 different areas of the skin. We examined whether the exotoxin (staphylococcal enterotoxin [SE]A, SEB, SEC, SED, and toxic shock syndrome toxin-1) could be detected. RESULTS: The levels of SEB-specific IgE were correlated with the severity of AD. Five of 6 patients having very high SEB-specific IgE antibody titers were under 6 years of age, and SEB was most frequently isolated (41%). There was no difference in severity between patients with or without exotoxin-producing S aureus. The severity of 9 patients who had both exotoxin-producing S aureus on the skin and specific IgE antibody against the same exotoxin in sera was significantly higher than that of the other patients. CONCLUSIONS: Anti-SEB IgE titers correlate well with the severity of AD. The presence of exotoxin-producing S aureus may precipitate AD through its specific IgE antibody.

Detection of K-ras mutations of bronchoalveolar lavage fluid cells aids the diagnosis of lung cancer in small pulmonary lesions.

An increased prevalence of K-ras oncogene mutation in lung adenocarcinoma has been shown by PCR-primer-introduced restriction with enrichment for mutation alleles (PCR-PIREMA) experiments. In the present study we investigated whether this method is useful for the diagnosis of lung cancer in small pulmonary lesions, which are difficult to diagnose cytologically as lung cancer by bronchoscopic examination. We examined bronchoalveolar lavage fluid (BALF) cells from 33 patients with single nodular pulmonary lesions of less than 2 cm in diameter (measured on chest computed tomography scans) for K-ras (codon 12) mutation, by PCR-PIREMA. Transbronchial fiberscopic examinations had not revealed lung cancer cytologically in any of the patients. The final diagnoses for the 33 lesions were 20 adenocarcinomas, 5 cases of focal fibrosis, 5 cases of pneumonia, 1 case of tuberculosis, 1 hamartoma, and 1 case of lymph node swelling. BALF cell lysates were amplified and digested with a restriction enzyme to detect the K-ras oncogene. Only the normal K-ras was observed after the first amplification and digestion for each of the 33 patients. Three amplifications and digestions were performed for each sample. We detected mutation of K-ras in BALF cells from 15 (75%) of 20 lung cancer patients and in cells from only 4 (31%) of 13 patients with nonmalignant lesions. The detection rate of the K-ras mutation in lung cancer was significantly greater than that in nonmalignant lesions (P = 0.012). Our results indicate that the detection of the codon 12 K-ras mutation in BALF cells by PCR-PIREMA aids the diagnosis of lung cancer in patients with small pulmonary lesions with negative cytological findings.

A feasibility study of continuous etoposide infusion combined with thoracic radiation for non-small cell lung cancer.

We conducted a feasibility study of continuous etoposide infusion, which was expected to suppress DNA repair after radiation, combined with radiation in patients with advanced non-small cell lung cancer (NSCLC). Between July 1995 and January 1997, 10 patients with NSCLC were registered. Thirty-six mg/m2/day etoposide was infused continuously for a mean of 19 days (range 14-26). Patients tolerated a mean total dose of accelerated hyperfractionated thoracic radiotherapy (1.5 Gy twice per day) of 52.6 Gy (range 33-60). The primary tumors of 7 patients showed partial responses and distant metastasis progression occurred before primary tumor progression in all 7 responders. The hematological adverse effects of chemoradiotherapy were grade 3 or 4 leukopenia in all 10 patients, grade 3 anemia developed in 3, and 2 had grade 3 thrombocytopenia. Six patients contracted infections and one of them died of pneumonia. The major non-hematological adverse effect was esophagitis, which was grade 3 in 3 patients, one of whom died of renal dysfunction. The serum etoposide concentrations were 1.6-2.0 microgram/ml, except in one patient, who had liver dysfunction due to B-type hepatitis. DNA repair gene XRCC1 mRNA expression in peripheral blood mononuclear cells was analyzed, using the reverse transcriptase-polymerase chain reaction, in 8 patients and was suppressed during etoposide infusion in 2. No relationship was observed between serum etoposide concentration and XRCC1 expression and clinical outcome. In conclusion, continuous etoposide infusion combined with thoracic radiation induces severe toxicity and should be given only after careful consideration.

Early monocytopenia after chemotherapy as a risk factor for neutropenia.

Neutropenia is a major adverse effect of cancer chemotherapy and sometimes causes life-threatening events. The present study was therefore conducted to identify risk factors for such neutropenia. Forty patients who had received chemotherapy at 3- or 4-week intervals for advanced lung cancer from May 1991 through February 1997 were analyzed retrospectively. Thirty-seven of the patients had received cisplatin-based chemotherapy. The mean neutrophil count on days 6 to 8 in 32 patients who developed grade 3 or 4 neutropenia during chemotherapy was not significantly different from that in eight patients who developed grade 1 or 2 neutropenia during chemotherapy. However, the mean leukocyte and monocyte counts on days 6 to 8 in the 32 patients with grade 3 or 4 neutropenia (5,181 +/- 1,830/microl and 87 +/- 84/microl, respectively) were significantly lower than those in the eight patients with grade 1 or 2 neutropenia (7175 +/- 1671/microl and 248 +/- 127/microl, respectively; p = 0.008 and p = 0.0001). Moreover, all 30 patients with a monocyte count of less than 150/microl on days 6 to 8 had grade 3 or 4 neutropenia and 8 of 10 patients with a monocyte count of 150/microl or higher on days 6 to 8 had grade 1 or 2 neutropenia, despite the absence of a correlation between the leukocyte count on days 6 to 8 and the neutrophil nadir. We conclude that a monocyte count of less than 150/microl on days 6 to 8 may be a predictor of grade 3 or 4 neutropenia during cancer chemotherapy at 3- or 4-week intervals (sensitivity 94%, specificity 100%).

[Pulmonary function after allogeneic hematopoietic stem cell transplantation].

This study was undertaken to identify the factors influencing pulmonary function in patients who underwent hematopoietic stem cell transplantation (HCT). Pulmonary function tests were evaluated before and after HCT in 51 adult patients who underwent HCT between 1993 and 1998. The patients with hematologic malignancies were given total body irradiation. Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine A and short-term methotrexate. Six patients suffered from acute GVHD above grade II and 27 patients suffered from chronic GVHD. The post-transplant % diffusing capacity (%DLco) 100 days after HCT was significantly lower than pretransplant values (82 +/- 21% versus 71 +/- 15%, p < 0.01). The %DLco at 100 days was significantly lower in patients with chronic GVHD than in patients without chronic GVHD (66 +/- 16% versus 77 +/- 9%, p < 0.05). These findings suggested chronic GVHD is related to the decreased %DLco values observed 100 days after HCT.

Gene-specific damage produced by topoisomerase inhibitors in human lung cancer cells and peripheral mononuclear cells as assayed by polymerase chain reaction-stop assay.

We have previously reported that the polymerase chain reaction (PCR)-stop assay is an useful technique for investigating gene-specific damage induced by cisplatin, and that the degree of gene-specific damage sustained by peripheral blood mononuclear cells (MNC) when exposed to cisplatin in vitro predicts the response to cisplatin-based chemotherapy. In the current study, we investigated whether PCR-stop assay was suitable for investigating gene- specific damage induced by the topoisomerase I inhibitor CPT-11 or the topoisomerase II inhibitor VP-16, in the human lung cancer cell lines PC-7 and H69, respectively. The cells were incubated with CPT-11 or VP-16 for 24 hours in vitro and the hypoxanthine-phosphoribosyl transferase gene was amplified by PCR. Amplification of a 2.7kb fragment of this gene was clearly inhibited by each drug in a dose dependent manner. The concentration which reduced amplification by 63% (D63, the dose that produces an average of one lesion per single strand of the 2.7kb fragment), was 318 micrograms/ml for PC-7 treated with CPT-11 and 35 micrograms/ml for H69 treated with VP-16. We also used PCR-stop assay to investigate gene-specific damage induced by CPT-11 or VP-16 in adenocarcinoma cells from pleural effusions and MNC from freshly isolated blood obtained from 4 patients with lung cancer. Between-patient variations in the extent of gene-specific damage were observed in both types of cells. These results suggest that PCR-stop assay is suitable for the analysis of interindividual variations in the extent of gene-specific damage induced by topoisomerase inhibitors in human cells.

[CT-guided localization for thoracoscopic pulmonary wedge resection].

Recently the identification of small-sized peripheral lung lesions has rapidly increased due to advancements in roentgenology. But for smaller lesions, definitive diagnoses by means of transbronchial or percutaneous biopsy have become more difficult. So we must resort to thoractomic or thoracoscopic biopsy. However, for thoracoscopic surgery palpation is inadequate, so the identification of deep or small lesions is difficult. Thoracotomy seems to be too invasive when used only for examination and not for therapy. Therefore, we tried CT-guided localization for thoracoscopic pulmonary wedge resection. Thus far we have performed CT-guided localization in 24 cases. Immediately prior to thoracoscopic surgery we placed marking devices in or beside the lesions after percutaneous puncture. As marking devices we used Kopans spring hook wire or a Naruke point marker. Pathological diagnoses of these lesions indicated 13 primary lung cancers (11 adenocarcinomas, 1 carcinoid, 1 squamous cell carcinoma), 4 focal fibroses, 2 metastases of renal cell carcinoma, 1 hamartoma, 1 tuberculoma, 1 cryptococcosis, 1 interstitial pneumonia, and 1 subpleural lymph node. The tumor diameters at their greatest dimension ranged from 3 to 33 mm (9.0 +/- 6.6 mm). The distance from the viceral pleura to the tumor surface ranged from 0 to 24 mm (10.9 +/- 6.7 mm). In one case pneumothorax occurred due to the shallow position of the tumor and the loss of the marking device. If these problems (pneumothorax, bleeding, loss of marking devices and others) are prevented, CT-guided localization should be performed as soon as possible before surgery. The identification of small peripheral lesions can almost be determined by CT now, so such identification may be the most reliable technique to employ during surgery.

[CT-image analysis of resected peripheral adenocarcinomas of the lung less than 1 cm in diameter].

Conventional CT (10-mm thick) and helical thin-section CT (2-mm thick) high-resolution images were obtained to study the relationship between the appearance of small peripheral adenocarcinomas of the lung and pathological findings. Eleven cases in which adenocarcinomas less than 1.0 cm in diameter were resected were retrospectively reviewed. Conventional CT images revealed air spaces within pulmonary nodules in 82% of tumors, an ill-defined margin in 91%, and involvement of vessels in 91%. When these findings are observed in pulmonary nodules, thin-section CT should be used for further examination. Helical thin-section CT images showed inhomogeneous internal attenuation (91%), irregularly undulating margins (91%), and vascular involvement (100%).