A randomized phase III trial of postoperative adjuvant therapy for completely resected stage IA-IIIA lung cancer using an anti­angiogenetic agent: irsogladine maleate.

AIM: Although angiogenesis plays an important role in the invasion and metastasis of solid tumors, very few anti-angiogenetic drugs have been developed. Reexamining the anti-angiogenetic effects of existing drugs such as Thalidomide is another possible strategy for drug discovery. Irsogladine maleate (IM) is a drug invented to treat gastric ulcers; however, several reports have shown that IM also exerts anti-angiogenetic effects in vitro, in vivo and in humans. In order to elucidate whether treatment with IM would improve the prognoses of patients with resected lung cancer, we conducted a randomized trial. METHODS: In the control group, uracil-tegafur (250 mg/m2/day) was administered for two years to patients with resected stage IB - IIIA lung cancer, and no adjuvant therapy was administered to those with stage IA disease. In the study group, IM (4 mg/body/day) was additionally administered for two years. RESULTS: No significant differences were observed in the major prognostic factors among 305 eligible patients between the study and control groups. Adverse effects were minimal. The overall survival of the patients in the study and control groups were not statistically different. When the analysis was stratified by regimen, among the patients with resected stage IA disease, disease-specific survival in the study group was slightly higher than that in the control group; however, the difference was not significant (p=0.07). CONCLUSION: Although it could not be proven that IM improves the prognoses of resected lung cancer patients, IM might have some effect on resected stage IA disease, and another trial should be conducted.

[Spontaneous regression of thymoma; report of a case].

A 44-year-old woman was admitted to our hospital with chest pain. Chest roentgenograms and computed tomography (CT) scan revealed an anterior mediastinal tumor and bilateral pleural effusion. However, CT scan 3 days after magnetic resonance imaging (MRI) revealed regression of the tumor. Extended thymo-thymectomy was performed via median sternotomy. The tumor was in the right lobe of the thymus. Pathologically the tumor was diagnosed as a mixed type non-invasive thymoma, but some parts of the tumor cells were necrotic. This is the 10th case of spontaneous regression of thymoma reported in the Japanese literature.

[Radiofrequency ablation for metastatic lung tumor].

BACKGROUND: Radiofrequency ablation (RFA) is a thermal ablation technique which results in coagulative necrosis. Several preliminary studies have evaluated the efficacy of RFA for liver tumor and benign prostate disease, but few studies for lung tumor. We experienced RFA for a metastatic lung tumor and it was effective. CASE: A 61-year-old woman was admitted to our hospital with chest pain. Extended thymothymomectomy with lymph node dissection was performed after diagnosis of thymic carcinoid. After 14 months, multiple small lung nodules, which had been 5-10 mm in diameter, were appeared and resected. However, 23 months after the first operation and 14 months after the second operation, multiple small lung nodules were appeared again and RFA was performed for 1 tumor without any complications. We used RITA 500 PA (RITA Medical Systems, INC.) and quadruple-hook radiofrequency probe with electrodes. Under local anaesthesia and ultrasound guidance, the probe was inserted into the target tumor and the hooks were deployed. The tumor became smaller (35 mm to 25 mm in diameter) in 2 months. CONCLUSION: RFA is an effective and minimally invasive technique to destruct local tumors.

A decrease in the amount and function of inhibitory GTP-binding protein in the resistance small artery from spontaneously hypertensive rats.

The inhibitory GTP-binding protein (Gi protein) plays an important role in regulation of vascular tone. Many studies have implicated the role of Gi protein in conduit vessels. However, the physiological role of Gi protein in the control of peripheral microvascular tone in hypertension has not been established yet. Therefore, we investigated the concentration of Gi protein in the peripheral resistance arteries and aorta in the spontaneously hypertensive rats (SHR), normotensive Wistar-Kyoto rats (WKY) and renovascular hypertensive rats (RHR), using immunohistochemical methods semiquantitatively. Changes in the function of Gi protein in relation to alpha2-adrenoceptor were also investigated by microcannulation techniques. We have shown that the amount of alpha2 subunits of Gi protein in the cremaster small artery was significantly lower in SHR aged 4 weeks and older than in age-matched WKY and that there were no significant differences between RHR and WKY. We also demonstrated that the function of Gi protein in relation to alpha2-adrenoceptor was already lower in SHR before the onset of hypertension. The quantitative and functional decline in Gi protein in the smooth muscle cells of peripheral small arteries were observed in SHR even before the onset of hypertension, whereas rats with secondary hypertension did not exhibit this finding.

Increased function of the voltage-dependent calcium channels, without increase of Ca2+ release from the sarcoplasmic reticulum in the arterioles of spontaneous hypertensive rats.

It has been reported that the increased function of the voltage-dependent calcium channels (VDCC) in the artery is involved in the increase of peripheral resistance in hypertension, and that the sarcoplasmic reticulum (SR) in the artery plays an important role in preventing the development of hypertension via a buffering effect. However, no reports have described the role of VDCC and SR in resistance arterioles in the development or maintenance of hypertension. We investigated the function of VDCC and of SR in the cremaster arterioles of spontaneous hypertensive rats (SHR) and age-matched Wistar Kyoto rats (WKY). The changes in diameter and the intracellular calcium ion concentration ([Ca2+]i) in the microdissected arterioles, using fluorescent dyes, were measured with videomicroscopy. The KCl concentration-response curves were analyzed in 4- to 5- and 7- to 8-week-old SHR and WKY. The changes in the vascular diameter and [Ca2+]i in response to ryanodine, an alpha-1 adrenoceptor, and angiotensin-II stimulation were compared between the 7- to 8-week-old SHR and WKY. We found an increase in the Ca2+ influx by VDCC in the early hypertensive stage, but not in prehypertensive SHR. However, after the onset of hypertension, there were no significant differences from WKY in the SR function mediated by Ca2+-induced Ca2+ release or inositol 1,4,5-trisphosphate-induced Ca2+ release. In conclusion, an increased influx of Ca2+ in the cell membrane, without a buffering effect of SR, was associated with progression of hypertension in the cremaster arterioles of SHR.

Integrating cultural values, beliefs, and customs into pregnancy and postpartum care: lessons learned from a Hawaiian public health nursing project.

Determining the elements of culturally competent health care is an important goal for nurses. This goal is particularly integral in efforts to design better preventive health care strategies for pregnant and postpartum women from multiple cultural and ethnic backgrounds. Learning about the values, beliefs, and customs surrounding health among the targeted groups is essential, but integrating this knowledge into the actual health care services delivery system is more difficult. The success of a prenatal and postpartum program developed for native Hawaiian, Filipino, and Japanese women in Hawaii has been attributed to the attention on training, direct care giving, and program monitoring participation by local cultural and ethnic healers and neighborhood leaders living in the community, with coordination by public health nurses. This article profiles central design elements with examples of specific interventions used in the Malama Na Wahine or Caring for Pregnant Women program to illustrate a unique approach to the delivery of culturally competent care.

Enhanced myogenic response in resistance small arteries from spontaneously hypertensive rats: relationship to the voltage-dependent calcium channel.

To characterize the myogenic response during the development of hypertension, we evaluated the myogenic response of small arteries isolated from the cremaster muscle of spontaneously hypertensive rats (SHR) aged 4-5 and 7-8 weeks, as compared with age-matched Wistar-Kyoto rats (WKY), using an in vitro system. The myogenic response of SHR aged 7-8 weeks (but not those aged 4-5 weeks) significantly exceeded that of WKY. Measurement of intracellular levels of free calcium ([Ca2+]i) in small arteries of the 7-8-week-old SHR and WKY loaded with a calcium-sensitive dye showed that the increase in [Ca2+]i in SHR was significantly greater than that in WKY during the myogenic response. The inhibitory effects of nitrendipine on the increased myogenic response and [Ca2+]i were greater in SHR. Thus, the myogenic response was enhanced in SHR and may be explained in part by an increase in Ca2+ entry through the voltage-dependent calcium channel (VDCC). The myogenic response and Ca2+ entry through the VDCC may be increased in association with the elevation of blood pressure.

Stimulatory guanine nucleotide-binding protein in failing heart of hamsters and rats.

The role of the stimulatory guanine nucleotide-binding protein (Gs) in heart failure is unclear. We therefore determined the amount of protein and mRNA of Gs in the failing myocardium using two animal models: the BIO 53.58 hamster, a model of genetic cardiomyopathy, and adriamycin-treated rats (ADR rats), a model of secondary cardiomyopathy. The maximal number of myocardial beta-adrenoceptors in the BIO 53.58 hamsters as well as in the ADR rats was significantly lower than that in the respective controls, indicating that the beta-adrenoceptors were down-regulated in heart failure. Analysis by Western blot and Northern blot revealed a significant decrease in Gs protein and mRNA in the BIO 53.58 hamsters relative to the control. There were no differences in the level of Gs protein or mRNA in the ADR rats vs the controls. The functional activity of Gs was investigated by measuring adenylate cyclase activity. The activity of adenylate cyclase in response to stimulation by sodium fluoride or forskolin was decreased in the BIO 53.58 hamsters relative to control animals, whereas no differences were observed in the ADR rats vs the controls. Thus, alterations in Gs in the failing heart appear to differ according to its cause.

The role of guanine nucleotide binding proteins in hamsters with myocardial hypertrophy.

To clarify the role of the guanine nucleotide binding proteins (G-proteins) in the pathogenesis of myocardial hypertrophy, we investigated the alterations in myocardial G proteins in 20-week-old F1b hamsters with pressure overload induced for 3 days (3-day AS), 7 days (7-day AS) and 14 days (14-day AS) by the stenosis of the abdominal aorta, and in 4- and 20 week-old BIO 14.6 Syrian hamsters (4-wk and 20-wk BIO) with genetic myocardial hypertrophy. The hearts of 7-day AS, 14-day AS and 20-wk BIO with left ventricular hypertrophy exhibited a decrease in the mRNA levels detected by Northern blot analysis and protein levels of G protein detected by Western blot analysis as compared with sham-operated and age-matched F1b hearts. The function of Gs or Gi showed a concomitant reduction in both models of myocardial hypertrophy. The hearts of 3-day AS and 4-wk BIO without myocardial hypertrophy showed no changes in G proteins as compared with sham-operated and age-matched F1b hearts. These results suggest that a decrease in G proteins is not involved in the pathogenesis of myocardial hypertrophy, but that myocardial hypertrophy reduced the G proteins.

[Surgical treatment of lung cancer over 80 years of age: investigation from post operative complications].

Seventeen patients with lung cancer over 80 years were treated surgically from 1983 through 1993 in our department. Thirteen patients were male and four were female. The histology of the tumor was adenocarcinomas, squamous, large and small cell carcinomas, in 9, 6, 1 and 1 cases, respectively. More than single lobectomy was performed in each patient. Unilateral pulmonary occlusion test was applied in patients whose expected contralateral FEV1.0/BSA was less than 800 ml.m2, or expected residual FEV1.0/BSA was less than 850 ml.m-2. Postoperative cardiovascular complications, such as PAT, PAC, PVC or Af, were seen in 9 patients, respiratory problems, namely, sputa retention, retained secretions or atelectasis, in 7 patients. Blood chemistry and hematology were performed for about three weeks after operations, and found increases in serum transaminases, and leukocytosis. However, there were no operative death. We conclude that some patients over 80 years of age are candidates for surgery after careful cardiopulmonary preoperative evaluation.

Messenger RNA for the guanine nucleotide-binding regulatory protein (G protein) is reduced in the acute ischemic myocardium.

It has been reported that the function of the guanine-binding regulatory protein (G protein), especially the alpha subunit of the stimulatory G protein (Gs alpha), in myocardium is decreased with acute ischemia. However, it is unclear whether this decrease is due to transcriptional or post-transcriptional changes. Moreover, no studies have examined the distribution of G protein mRNA in ischemic myocardium using in situ hybridization. The purpose of this study was to explore alterations in mRNA of G proteins (Gs and Gi) in ischemic hearts using in situ hybridization. We measured the levels of mRNA for Gs alpha and Gi alpha in ischemic and non-ischemic myocardium by in situ hybridization using a radioisotope imaging system. We compare these mRNA levels in ischemic and non-ischemic myocardium with Northern blot analysis and the protein levels of G proteins by Western blot analysis. The mRNA for Gs alpha and Gi alpha was distributed diffusely in normal hearts. Levels of mRNA detected by in situ hybridization were substantially reduced by acute ischemia, and these results were confirmed by Northern and Western blot analysis. These results suggest that decreased levels of mRNA and protein for G proteins may underlie the impaired function of the receptor--G protein--adenylate cyclase system in ischemic myocardium. In addition, quantitative evaluation of mRNA is possible by in situ hybridization and correlates well with Northern analysis.

Improvement of pancreaticojejunostomy in pancreatoduodenectomy.

We compared two methods of pancreaticojejunostomy in 36 patients undergoing pancreatoduodenectomy. Pancreatoduodenectomy was performed in 17 men and 19 women aged 35-81 years, including 20 with pancreatic head cancer and 11 with papilla of Vater cancer. Group A (n = 19) underwent pancreaticojejunostomy with a stent tube that was exteriorized via the jejunum. In group B (n = 17), the stent tube ran transhepatically from the pancreatic duct before being exteriorized. The operating time, volume of pancreatic secretions, and time until stent removal were not significantly different between the two groups. However, there were 3 deaths related to early anastomotic leakage and 1 pancreatic fistula in group A, while group B had only 2 spontaneously healing pancreatic fistulas. Our results suggested that the pancreaticojejunostomy method used for group B is superior due to its simplicity, shorter operating time, and better outcome.

[A case of lung cancer combined with ocular myopathy and idiopathic thrombocytopenic purpura which was presumed to be caused by heart catheterization].

A 61-year-old patient was admitted to our hospital because of a chest abnormal shadow. He was suffered from ocular myopathy for more than 4 years. A lab data on the admission showed only a slight thrombocytopenia. After the unilateral pulmonary arterial occlusion test for the preoperative evaluation of thoracotomy, the hemorrhagic tendency was appeared. A detailed examination proved idiopathic thrombocytopenic purpura which was presumed to be caused by the heart catheterization. We employed high-dose intravenous gamma-globulin infusion and concentrated platelet transfusion for 5 days for preventing hemorrhagic complications during the thoracotomy. The partial resection was undergone for the left upper lobe tumor, which was proved as large cell carcinoma. The postoperative hemorrhage was well controlled. We conclude that the high-dose intravenous gamma-globulin infusion and/or concentrated platelets transfusion should be positively employed for the patients with even slight thrombocytopenic purpura.

[Changes in right ventricular hemodynamic function by unilateral pulmonary arterial occlusion test].

We performed unilateral pulmonary arterial occlusion test (UPAO) for the preoperative evaluation of lung function in patients undergoing lung resection. In this test, the main pulmonary artery of either side is occluded to simulate postoperative functional status. In order to evaluate the right ventricular hemodynamic function, we measured right ventricular ejection fraction (RVEF) and right ventricular end-diastolic volume index (RVEDVI) throughout UPAO by thermodilution method. We investigated the relationships between changes in right ventricular hemodynamic function and postoperative complications related to cardiac functions, namely arrhythmias or heart failure. Thirty-four patients without heart disease prior to lung resection were examined by UPAO, and RVEF and RVEDVI were measured. Analyses demonstrated that changes in RVEF were inversely correlated with changes in RVEDVI. In 6 cases, RVEDVI increased from control by over 20% during UPAO. All of these patients had postoperative cardiac complications. The hypothetical ventricular function curves showed a large increase in RVEDVI relative to right ventricular stroke work index (RVSWI), suggesting a decrease in right ventricular function. In conclusion, these results suggest that changes in RVEDVI during UPAO may predict postoperative cardiac complications in patients undergoing pulmonary resection.

[Chronic pulmonary mucormycosis diagnosed by bronchoscopy: a case report].

A 56-year-old man with bronchial asthma and diabetes was admitted with massive hemoptysis and thick-walled cavity in the right middle lung field on chest X-ray films. He had been treated with antibiotics for eight months under the diagnosis of lung abscess before his admission. After occlusion of the bronchial arteries with metallic coils, bronchofiberscopy was performed disclosing the obstruction of right B3b. Microscopic examination of bioptic material and bronchial brushing smear taken from right B3b yielded numerous broad, nonseparate hyphae. Right middle and lower lobectomy were performed under a diagnosis of chronic pulmonary mucormycosis. The patient was recovered and discharged on 55 th days after operation.

Prenatal and postpartum care in Hawaii: a community-based approach.

Given the problems of access, retention, and relevant prenatal care content, supplements to existing programs for health-care delivery during pregnancy and after birth are necessary. This article describes a community-based approach to prenatal and postpartum care that has been developed to address these issues. Culturally sensitive strategies were created for use with Hawaiian, Filipino, and Japanese women living on the island of Hawaii. Six nursing care and community outreach interventions were used. Local public health nurses assisted in developing the program and are responsible for its coordination and implementation.

[Extension of functional limitation for surgery of lung cancer by unilateral pulmonary arterial occlusion test].

We performed unilateral pulmonary arterial occlusion test to determine the indication for lung resection functionally, and investigated 32 cases whose total pulmonary vascular resistance was over 700 dyne.sec.cm-5/M2. Thirteen out of 32 cases underwent surgery. There was no difference in lung function tests between surgical and non-surgical cases. Nine out of 12 cases whose pulmonary vascular resistance was less than 800 dyne by unilateral pulmonary arterial occlusion test underwent surgery, and none of these cases died within 3 months after surgery. In non-surgical cases, two were aged patients and one had chronic renal failure. Four out of 20 cases whose total pulmonary vascular resistance was over 800 dyne underwent surgery. Two cases that underwent surgery died within 3 months after surgery. These results suggest that the functional limitation of lung resection can be extended from 700 dyne.sec.cm-5/M2 to 800 dyne.sec.cm-5/M2 total pulmonary vascular resistance by application of unilateral pulmonary arterial occlusion test.

[Surgery for the patients whose total pulmonary vascular resistance was over 700 dyne during unilateral pulmonary artery occlusion test].

To determine the indication for surgery from the point of pulmonary function, we have performed the unilateral pulmonary artery occlusion test in lung cancer patients. In these patients, we gave a surgery in 13 cases whose total pulmonary vascular resistance were over 700 dyne.sec.cm-5/M2 per body surface area. The pulmonary hemodynamics before and during pulmonary artery occlusion were 549 +/- 82 and 798 +/- 78 dyne.sec.cm-5/M2 in total vascular resistance, 18.7 +/- 3.8 and 27.2 +/- 4.3 cmHg in mean pulmonary arterial pressure and 2.69 +/- 0.36 and 2.73 +/- 4.3 L/min/M2 in cardiac index respectively. In 7 cases out of 13, we performed selective pulmonary artery occlusion test. In pulmonary function test, 10 cases had a chronic obstructive diseases, 2 cases had a disturbance of diffusion and one case has a contractive disease. We gave a lobectomy in 12 cases and completion pneumonectomy in one case. Two of lobectomy cases died in the early phase: 42 and 72 days after surgery due to pulmonary complications. One of these cases needed an additional completion pneumonectomy because of bronchial fistel. Surgical complications were seen in 12 cases. These 13 cases used to be recognized that they have no indication of surgery because of low pulmonary function, however it revealed that we can give a lobectomy through a high intensive care after surgery.

Adaptation themes for prenatal care delivered by public health nurses.

An adaptation process involving three cognitive themes provides the framework for community nursing model for prenatal care on the island of Hawaii. The themes are based on the cognitive adaptation model developed by Taylor (1983) and include search for meaning, sense of mastery, and self-esteem. Each theme is used to guide public health nurses and is identified during designated encounters between the nurse and woman throughout the duration of prenatal care. A focus on adaptation themes for each trimester of pregnancy expands on the medical model of prenatal care to highlight developmental processes of childbearing and broaden the scope of practice for public health nurses responsible for assessment and intervention in the community.

The first report of a case with acute myocardial infarction showing familial deficiency of creatine kinase.

A 46-year-old male patient was diagnosed as suffering from acute myocardial infarction, but his serum creatine kinase (CK) level was extremely low and no CK isozymes were detected in the serum. The total CK activities in the skeletal muscle amounted to only 2% of that of the control. Electrophoresis of the CK isozymes in the skeletal muscle showed that CK-MM was absent but the CK-BB and abnormal isozyme bands were present. There was no evidence of myocardial ischemia, although the exercise treadmill test revealed ST segment depression in the chest leads. One of the patient's sisters had an extremely low serum CK level suggesting inheritance of this abnormality. This is the first report of a case showing familial deficiency of CK.