Life-threatening airway obstruction due to retropharyngeal and cervicomediastinal hematomas following stellate ganglion block.

Airway obstruction by retropharyngeal or cervicomediastinal hematomas following stellate ganglion block is life-threatening. The onset of the initial symptoms of retropharyngeal or cervicomediastinal hematoma usually occurs 2 hours or more after stellate ganglion block. We report the rare complication of airway obstruction leading to respiratory arrest caused by retropharyngeal and cervicomediastinal hematomas due to rebleeding of an ascending cervical artery 3 days after stellate ganglion block.

Expression of periostin in patients with non-small cell lung cancer: correlation with angiogenesis and lymphangiogenesis.

The aim of this study was to evaluate periostin expression measured immunohistochemically in patients with non-small cell lung cancer (NSCLC) and to determine its association with clinical features, prognosis, angiogenesis, and lymphangiogenesis. We investigated periostin expression in a series of 88 patients with NSCLC. We also determined whether expression of periostin correlated with microvessel density and lymphatic microvessel density. Periostin was expressed in 42% of 88 patients. Its expression was significantly correlated with tumor size, lymph node metastasis, disease stage, and lymphatic invasion (p=0.0128, 0.0015, 0.0310 and 0.0273, respectively). There also was a significant relation between periostin expression and microvessel density and lymphatic microvessel density (all p<0.0001). Five-year survival rates were better in patients with negative periostin expression than in those with positive periostin expression (p=0.0044). Periostin expression was not significant in a multivariate additive model. Our findings show that periostin correlates with increased tumor progression and a worse prognosis in NSCLC, as well as with angiogenesis and lymphangiogenesis.

[Resected lung cancer with production of CA19-9].

We report 2 cases of resected CA19-9 producing adenocarcinoma of the lung. Immunohistochemical studies of the specimens in 2 cases showed positive staining for CA19-9 in most of tumor cells. The serum CA19-9 levels decreased after operations and effective chemotherapy in these cases. But the serum CA19-9 levels increased with regrowth of tumors or with no therapeutic gain by chemotherapy. The serum CA19-9 level was useful to evaluate the therapeutic effect of surgery and chemotherapy, and may be effective in detecting the recurrence of lung cancer.

Purification and mode of action of a microsomal endoribonuclease from rat liver.

An endoribonuclease has been purified nearly to homogeneity from rat liver microsomes, and its mode of action and general properties were studied. The enzyme had an apparent molecular weight of 58 000, as estimated by both gel filtration and SDS-polyacrylamide gel electrophoresis and produced oligonucleotides from poly(A), poly(U) and poly(C). No mononucleotide was obtained by the enzymatic hydrolysis of the above substrates. The enzyme made endonucleolytic cleavages which generated 5'-phosphate-terminated oligonucleotides. It was suggested that the existence of at least (Ado5'P)2 residues at both sides of the cleavage bond was necessary for the action of the endoribonuclease. Divalent cations (Mg2+ or Mn2+) were required for the enzymatic activity, while K+ inhibited the enzyme. Spermine stimulated the enzymatic activity in the presence of 1 mM Mg2+.

Corneal advanced glycation end products increase in patients with proliferative diabetic retinopathy.

OBJECTIVE: To evaluate corneal advanced glycation end product (AGE) fluorescence in patients with diabetes and in healthy control subjects. RESEARCH DESIGN AND METHODS: Corneal autofluorescence was measured in 26 eyes of 26 patients with type 2 diabetes (mean age 57.0 years; mean disease duration 12.2 years; mean HbA1c 7.1%) and 13 eyes of 13 healthy age-matched control subjects (mean age 57.9 years). The patients with type 2 diabetes were divided into the following groups: patients without diabetic retinopathy (DR), patients without proliferative diabetic retinopathy (PDR), and patients with PDR. Corneal autofluorescence was measured by fluorophotometry with the wavelength that is characteristic of AGE fluorescence (excitation and emission 360-370 nm and 430-450 nm, respectively). We defined peak corneal autofluorescence levels as corneal AGE fluorescence values. We compared the corneal AGE fluorescence values in the four groups. RESULTS: In the PDR group (11.9 +/- 3.9 arbitrary units [mean +/- SD]), the corneal AGE fluorescence values were significantly higher compared with the control subjects (6.9 +/- 1.3 arbitrary units), the patients without DR (7.4 +/- 2.1 arbitrary units), and the patients without PDR (6.9 +/- 2.2 arbitrary units) (P < 0.05). CONCLUSIONS: We found that corneal AGEs may increase in patients with diabetes and PDR compared with control subjects, patients without DR, and patients without PDR. In the patients with PDR, increased corneal AGEs may play a role in diabetic keratopathy.

Arterial injury-induced smooth muscle cell proliferation in rats is accompanied by increase in polyamine synthesis and level.

Proliferation of smooth muscle cells (SMC), enhancement of polyamine biosynthesis and increase in polyamine level in response to deendothelialization in the rat aorta were studied. [3H]Thymidine incorporation into SMC in aortas denuded with a balloon catheter began 25 h after injury, and maximal incorporation occurred 33-37 h after injury. Afterwards, [3H]thymidine incorporation declined, approaching the baseline level, but was slightly higher than that of sham-operated controls until 14 days after injury. Intimal thickening started 7 days after injury, and peaked at 21 days. Prior to these proliferative changes in aortic SMC, a rapid and transient increase in ornithine decarboxylase (ODC) activity was observed within 8 h after injury. There was no significant difference in ODC activity between injured and intact aortas after 4 days. The levels of polyamines, putrescine, spermidine, and spermine increased and were maximal at 48 h after injury, 8.1, 3.4 and 1.4 times the control levels, respectively. Increased levels of polyamines, in particular spermidine, continued until 7 days after injury. These results suggest that the enhancement of polyamine synthesis and the increased polyamine content of the aorta play important roles in the proliferation of SMC and in the development of intimal thickening, particularly in the initial proliferative response of medial SMC after deendothelialization.

Syntheses and effect of bombesin-fragment6-14 and its four analogues on food intake in rats.

A nonapeptide, H-Asn-Gln-Trp-Ala-Val-Gly-His-Leu-Met-NH2, corresponding to amino acids 6 to 14 of bombesin and its four analogues were synthesized by a solid-phase method and were tested for their comparative effect on reducing activity on food intake using male Wistar rats. The synthetic bombesin-fragment6-14 showed reducing effect on food intake using male Wistar rats. Of the synthetic analogues, [Phe(4F)13]bombesin-fragment6-14 exhibited the most potent effect. The reducing effect on food intake of [Sar11]bombesin-fragment6-14 was lower than that of our synthetic bombesin-fragment6-14, but the other two analogues, [betaAla11]bombesin-fragment6-14 and [1-Nal8]bombesin-fragment6-14 showed no reducing effect on food intake in rats.

Changes in blood-retinal barrier permeability in form deprivation myopia in tree shrews.

To study the correlation between blood-retinal barrier (BRB) permeability and development of form deprivation (FD) myopia, FD was induced in tree shrews. The refractive error and the axial dimensions of the optical elements were measured. Ocular fluorescence was measured before and after fluorescein-Na injection. The inward permeability (P(in)) of the BRB was measured before and 15, 30, and 45 days after FD was induced. FD eyes became significantly myopic 15 days after FD was induced (P<0.01), and myopia progressed 45 days after FD was induced compared with untreated controls. Neither anterior chamber length nor lens thickness changed significantly. The vitreous chamber in FD eyes, however, was significantly elongated from 15 days after FD was induced (P<0.01) compared with controls. The P(in) ratio (P(in) [FD eye]/P(in) [untreated control]), increased significantly 45 days after FD was induced (P<0.05). In FD myopia in tree shrews, the BRB permeability increases abnormally. Impaired BRB function might be a secondary effect of myopia development rather than the cause of myopia.

Changes in corneal and lens autofluorescence and blood glucose levels in diabetics: parameters of blood glucose control.

PURPOSE: We investigated corneal and lens autofluorescence in patients with proliferative diabetic retinopathy (PDR) to determine a correlation between the two parameters and blood glucose levels and HbA1c. METHODS: Corneal and lens autofluorescence levels in 17 PDR patients and 8 healthy controls were measured with a fluorophotometer fitted with an anterior segment adapter. We measured the lower blood glucose level (BS1), corneal autofluorescence (CA1), and lens autofluorescence (LA1) simultaneously and the higher blood glucose level (BS2), CA2, and LA2 simultaneously on the same day. We defined parameter changes as: delta BS = BS2 - BS1, delta CA = CA2 - CA1, and delta LA = LA2 - LA1. RESULTS: Corneal and lens autofluorescence significantly increased in the patients, compared with the controls (p < 0.001). Lens autofluorescence had a significant positive correlation with HbA1c (r = 0.656, p < 0.01) in the patients. delta CA (ngEq/ml) correlated significantly with delta BS (mg/dl) (r = 0.631, P < 0.01). CONCLUSIONS: Results suggest that lens autofluorescence might represent the long-term control of diabetes, and corneal autofluorescence levels may represent short-term changes in the blood glucose level, because hyperglycemia accelerates with increasing corneal autofluorescence in PDR patients. Corneal and lens autofluorescence may be related to the breakdown of the blood-aqueous barrier.

Thymoma with pemphigus foliaceus.

A 75-year-old Japanese woman was referred to us because of an anterior mediastinal mass. Crusts and shallow erosions developed 10 months earlier on her upper chest, back, and scalp. Pemphigus foliaceus was diagnosed based on histological examination of skin biopsy specimens and positivity for serum anti-desmoglein 1 antibody by enzyme-linked immunosorbent assay. Neurological examination and electromyography ruled out myasthenia gravis. Total thymectomy was performed, and the postoperative pathology studies showed mixed lymphoepithelial thymoma. One year after the resection, the eruption and alopecia improved and the serum anti-desmoglein 1 antibody titer decreased, suggesting a beneficial effect of thymectomy on thymoma-related pemphigus.

Fluorophotometry with a small animal adapter.

The usefulness of the Fluorotron Master fluorophotometer fitted with a small animal adapter was evaluated with tree shrews. We also determined that the optimal measurement parameters for these animals, which are regarded as promising for experimental use in ophthalmic research, are: fluorescein-Na concentration, 0.5 x 10(-9) to 1.0 x 10(-6) g/mL; fluorescein-Na dosage, 2 mg/kg; measurement time, 30 minutes after injection of fluorescein-Na into the ocular compartments. Results indicated that ultrafiltration for the measurement of protein-unbound fluorescein can be done with a hematocrit tube and a minimal blood sample, thereby reducing the impact of the sampling on the animal's general condition. The Fluorotron Master with the small animal adapter can offer advantages in estimating the blood-ocular barrier permeability using disease models in tree shrews.

[Early ocular changes in a tree shrew model of diabetes].

We developed a tree shrew model of diabetes using streptozotocin (STZ), and studied early ocular changes of diabetes (after one week of diabetes) by fluorophotometry. STZ was injected intraperitoneally at doses of sixty to 400 mg/kg body weight. Animals injected with more than 300 mg/kg of STZ developed diabetes. Corneal autofluorescence was significantly increased one week after STZ injection. These changes may be related to impairment of the ocular homeostatic mechanisms due to the onset of diabetes. Using this model, we might be able to obtain diabetic ocular impairment data closer to human data than in previous models of diabetes, because tree shrews are primates.

[Fluorophotometry of the animal eye].

We assessed the usefulness of the Fluorotron Master fitted with a small animal adapter. We also discuss the measurement conditions for the tupai, which is a promising experimental mammal. A good concentration for measurements with this instrument ranged from 0.5 x 10(-6) to 1.0 x 10(-6) g/ml. A suitable time for fluorophotometry of the tupai was 30 min. after injection of fluorescein-Na, and a suitable dose of the fluorescein-Na was 2 mg/kg. We could do ultrafiltration for measurement of the protein unbound fluorescein concentration from a minimal sample of the blood using a hematocrit tube, and thus could reduce the deleterious effects of blood sampling on the animal. This instrument is useful for the estimation of the blood-ocular barrier permeability of animal models.

[Order-made therapy for early lung cancer patients].

To give optimal treatment to the patients with early lung cancer, we are trying to establish two new techniques to select the patients of poor prognosis and sensitive to the chemotherapy. To pick up the patients of poor prognosis nevertheless the early stage of their lung cancer, we are developing a new method to detect cancer cells floating in the peripheral blood flow with RT-PCR using cancer specific mRNA. To choose optimal chemotherapy regimens, we have established a new chemosensitivity testing (collagen gel droplet embedded culture drug sensitivity test: CDDST) for non-small cell lung cancer (NSCLC). Median survival time (MST) of the patients (n = 11) with unresectable NSCLC, who were given optimal chemotherapy according to CDDST, was 15.8 months and MST of those (n = 16) who did not have any sensitive agents according to CDDST was 5.6 months. There was significant difference between these two groups (p = 0.0048; logrank).

[Clinical analysis in patients undergoing extended resection of pT3 non-small cell lung cancer].

Among pT3 cases there contain various subgroups in terms of the organ which is involved in. We analyzed medical records of 85 consecutive patients who underwent extended surgery with diagnosis of pT3 excluding interlober invasion. As regards to the site of invasion, there are not significant differences in survival between pleural invasion, chest wall involvement, pericardial invasion, and diaphragmatic invasion. However, survival of patients who showed involvement of main bronchus seemed better than other groups. Survival of pT3 cases are in part determined by lymph node involvement, N0 group showed 36.0% 5 year survival rate whereas N1 group 20.0%, and there are no patient with N2 disease who survived 5 years. Among pleural and chest wall involvement group, N0 group showed 34.2% 5 year survival and there are no survival in N1 and N2 group. As regards to histologic subgroups, there are not significant differences between each group. Thus we conclude that in pT3 cases, N0 cases are the best candidate for surgical resection, and that adjuvant therapy is necessary for those with N1 or N2 involvement. Cases with bronchial extension should not be argued in the same field of locally invasive lung cancer because of better survival.

[Clinical analysis of surgically resected multiple primary lung cancer].

Synchronous and metachronous lung cancer is occasionally encountered. Frequency of the occurrence is increasing because of recent progress of imaging technique such as high resolution CT and CT based annual lung survey. We analyzed clinical characteristics of both synchronous and metachronous lung cancer treated surgically in our facility. There were 20 cases of multiple lung cancer cases, which is consisted of 12 synchronous multiple lung cancer cases and 8 metachronous lung cancer cases. Mean age was 62 years old and there were 14 male and 6 female cases. Among synchronous group, 8 cases have multiple shadow in ipsilateral hemithorax and 4 cases in both side. Surgery was carried out according to the extent of the disease and lung reserve. Associated cancer was diagnosed stage IA or IB in all cases. Five-year survival was 58.9%. Meanwhile, as regards to metachronous group, mean interval between first cancer and second cancer was 73 months. Seven cases have contralateral second primary lung cancer and one case has ipsilateral second primary lung cancer. In 3 cases, histology of the first and the second disease were different and in 5 cases that were the same. The first procedures were complete resection with systemic mediastinal LN dissection. The second procedures were determined based on the lung reserve. Pathological stage of the second disease were either stage IA or IB. There were no operative mortality and 5 years survival was 75%. Since there is no operative mortality and the outcome seems satisfactory when the patient has enough lung reserve, aggressive surgical resection should be considered in the case of multiple primary lung cancer. There is an increasing chance of synchronous multiple primary lung cancer because of improvement of imaging system. We have to prepare new therapeutic strategy for those patients.

Prediction of anti-tumour effect of thermochemotherapy with in vitro thermochemosensitivity testing for non-small cell lung cancer.

PURPOSE: We investigated whether it is possible to predict the antitumour effects of thermochemotherapy from the results of anticancer agent sensitivity testing. MATERIALS AND METHODS: We produced a nude mouse cancer model using 4 lung cancer cell lines. Animals were divided into 4 groups: Thermotherapy (HT group), chemotherapy (CT group), thermochemotherapy (HT+CT group), and no therapy (NT group). Comparison of in vivo and in vitro effects were performed using cisplatin (CDDP), doxorubicin (ADR) and vinorelbine (NVB). In vivo thermotherapy was performed using the Thermotron RF IV, and radiofrequency (RF) capacitative hyperthermia device that induces a localised temperature of 42.0 degrees C for 45 min. The collagen gel embedded culture drug sensitivity test (CD-DST) was used for in vitro chemosensitivity analysis of the anticancer agents. In vitro thermochemotherapy was performed using a modified CD-DST method, with the incubator set at 42.0 degrees for the first hour of the 24 hours drug exposure period. RESULTS: A good correlation was seen between in vivo and in vitro treated/control ratios (T/C%) in the HT group (R = 0.91, p = 0.09). Good correlations were also seen between in vivo and in vitro T/C in all cell lines in the CT group (R = 0.759, p = 0.09) and the HT+CT group (R = 0.65, p = 0.02). True positive rate was 87.5% (7/8), and true negative rate was 100% (4/4). Sensitivity, specificity and accuracy were 100% (7/7), 80% (4/5), and 91.7% (11/12) respectively. CONCLUSION: A modified CD-DST using an exposure temperature of 42 degrees C can be used to predict the antitumour effect of thermochemotherapy.