A novel arterial infusion chemotherapy for the treatment of patients with advanced pancreatic carcinoma after vascular supply distribution via superselective embolization

BACKGROUND: Patients with American Joint Committee on Cancer Stage IV advanced pancreatic carcinoma have been treated by systemic chemotherapy, intraarterial chemotherapy, radiation therapy, and multidisciplinary treatment using a combination of these. However, the outcome has not always been satisfactory. In the current study the authors describe the method and results of a new chemotherapy for advanced pancreatic carcinoma. METHODS: To restrict the blood flow into the pancreas (mainly to the great pancreatic artery and the caudal pancreatic artery), the peripancreatic blood vessels were embolized superselectively with microcoils. In 31 patients with advanced pancreatic carcinoma, the catheter tip for the arterial infusion chemotherapy was placed in the splenic artery just proximal to the branching of the great pancreatic artery when the treatment was given for primary tumors, and in the common hepatic artery when the treatment was given for a metastatic liver lesion. The other end of the catheter was connected to an implanted injection port embedded in the femoral region, and 5-fluorouracil and cisplatin were administered by continuous arterial infusion. RESULTS: Of the 31 patients with advanced pancreatic carcinoma, 23 (74%) underwent hemodynamic change and arterial infusion chemotherapy, with a response rate of 73.9% (complete response rate of 8.7% and a partial response rate of 65.2%) and a mean survival period of 18.26 +/- 10.06 months. The 1-year, 2-year, and 3-year survival rates were 90.9%, 42. 8%, and 18.3%, respectively, with a mean survival period of 19.0 months. Of these 23 patients, the 16 patients with liver metastases had a response rate of 68.8% and a mean survival period of 16.25 +/- 8.35 months, whereas the 7 patients without liver metastases had a response rate of 87.5% and a mean survival period of 22.86 +/- 12.69 months. CONCLUSIONS: In patients with Stage IV advanced pancreatic carcinoma, arterial infusion chemotherapy after hemodynamic change was found to be effective against both primary tumors and metastatic liver lesions. The authors believe that the treatment presented in the current study should be attempted, even in patients with advanced pancreatic carcinoma, as long as the blood vessels for vascular supply distribution exist.     

Sequential internal mammary-coronary artery bypass

A total of ten patients have undergone sequential bypass grafting of the internal mammary artery (IMA) to the coronary arteries at Osaka Medical College. Operative procedures included left IMA bypass to the left anterior descending (LAD) artery and its major diagonal branch in six patients; to the obtuse marginal branch and diagonal branch in three patients; and to the first and the second diagonal branches in one patient. The right internal mammary artery was concomitantly utilized in 4 patients and saphenous vein graft was also utilized in 6 patients. Postoperative angiographic studies were performed in nine patients within 6 months after operation and in all 18 sites of IMA anastomoses, the IMA sequential grafts were patent. Since sequential IMA-coronary bypass technique means the increase of arterial graft, we believe that this technique should be used for multivessel coronary revascularization especially in younger patients.     

Analysis of non-histone chromatin proteins in porcine malignant hyperthermia

Non-histone chromatin proteins (NHCP) were isolated from skeletal muscle, left ventricle and liver of swine susceptible to malignant hyperthermia and from controls. These proteins were extracted with phenol buffers and fractionated by polyacrylamide gel electrophoresis. Isoelectrofocusing gel electrophoresis revealed quantitative differences in NHCP from skeletal muscle between disease and control groups. The high resolution of proteins by two-dimensional polyacrylamide gel electrophoresis showed a relative similarity between skeletal muscle, heart and liver although some differences could be discerned. Non-histone chromatin proteins of molecular weight 35,000–45,000, focusing between pH 7 and 9, were increased in skeletal muscle nuclei derived from malignant hyperthermia-susceptible swine. These proteins appear to be important in the maturation of messenger RNA. No alterations were seen in either heart or liver. We conclude that an increase in NHCP which is associated with the processing of messenger RNA, may be important in the phenotypic expression in skeletal muscle of malignant hyperthermia in swine.     

Maximum permissive dosage of lactose and lactitol for transitory diarrhea, and utilizable capacity for lactose in Japanese female adults

This study aims to estimate the tolerable lactose intake which can be utilized in the digestion by lactase and in the fermentation by intestinal microbes in Japanese female adults. The first, the maximum permissive dosage of lactose not to induce transitory diarrhea was estimated based on the oral ingestion of lactose at several dose levels in all the subjects, and compared with that of lactitol which is not hydrolyzed by digestive enzymes. A second lactose tolerance test involving 10 g and 30 g of lactose was carried out in 10 subjects showing resistance to diarrhea, and serum glucose and insulin levels and the amount of hydrogen excreted in the breath were measured for comparison with those of glucose and lactitol. Subjects were 43 Japanese female adults (average: age 20.5+/-2.1 y, weight 51.3+/-5.1 kg) who had not been diagnosed as having either hypolactasia or being lactose intolerant. Serum glucose and insulin levels were scarcely elevated following the ingestion of both 10 g and 30 g of lactose, while the amount of hydrogen excreted in the breath was greatly increased following the ingestion of 30 g of lactose, but these levels were less following the ingestion of 10 g of lactose. In contrast, the ingestion of 15 g of glucose significantly increased blood glucose and insulin levels, while no hydrogen was detected in the breath. The maximum permissive dosage of lactose not to induce transitory diarrhea was 0.72 g/kg of body weight and that of lactitol was 0.36 g/kg of body weight in Japanese adults. The digestive capacity of lactase is less than 10 g of lactose by single ingestion, while intestinal microflora are able to ferment approximately 20-30 g of lactose. In addition, the ingestion of more than 10 g of lactose might be contributed as prebiotics.     

Postoperative Size of the Right Ventricular Outflow Tract and Optimal Age in Complete Repair of Tetralogy of Fallot

One hundred forty-three patients underwent complete repair of tetralogy of Fallot with an overall mortality of 14.7%. The mortality rate correlated with the preoperative pulmonary artery to aorta (PA/Ao) diameter ratio but not with age. A retrospective study revealed that for success, the postoperative pulmonary annulus should be over 1.75 cm² per square meter of body surface area (BSA) in patients with a BSA of less than 0.6 m² at operation. The younger the patient, the lower was the ratio of right ventricular to aortic systolic pressure, even when the cross-sectional area index (CSAI) of the pulmonary annulus was the same. Even with application of an outflow patch, pulmonary regurgitation was negligible when the CSAI was less than 2.6 cm²/m². The pulmonary vascular response to increased blood flow was excellent in younger patients. Residual ventricular septal defect and recurrent pulmonary stenosis were unrelated to age.Thus, for symptomatic patients, even infants, we recommend that complete repair be attempted when the PA/Ao diameter ratio is over 0.3. For patients in whom this ratio is less than 0.3, operation should be undertaken when the average diameter index of the arterial pathway to the right upper lobe is above 4 mm/m². Should this index be less than 4 mm/m², a two-stage operation is recommended.     

Enhanced excitability of hippocampal mossy fibers and CA3 neurons under dietary zinc deficiency

On the basis of the evidence that susceptibility to kainate-induced seizures is enhanced by zinc deficiency and that glutamate concentrations in hippocampal extracellular fluid are excessively increased during seizures, excitability of hippocampal mossy fibers and CA3 neurons was examined using hippocampal slices, which were prepare from mice fed a zinc-deficient diet for 4 weeks. The spatio-temporal dynamics of zinc and calcium was monitored using their indicators, membrane-impermeable ZnAF-2 and membrane-permeable fura-2 AM, respectively. When the molecular layer of dentate gyrus was stimulated with 100mM KCl for 1s, the increased percentages of extracellular zinc in the stratum lucidum and CA3 pyramidal cell layer were higher in zinc-deficient mice than in the control mice, implying that glutamate release from the mossy fibers of the dentate granular cells is enhanced by zinc deficiency. Judging from the increased percentages, however, the amount of zinc released was estimated to be less in zinc-deficient mice. On the other hand, the basal calcium concentrations in the stratum lucidum and CA3 pyramidal cell layer detected with fura-2 were higher in zinc-deficient mice than in the control mice, indicating that hippocampal calcium homeostasis is affected by zinc deficiency. Furthermore, the increased percentage of intracellular calcium in the stratum lucidum by stimulation with high K+ was enhanced by the zinc deficiency. The alteration of hippocampal calcium homeostasis seems to enhance excitability of dentate granular cells in zinc deficiency, following by an enhanced excitability of postsynaptic structures in CA3 neurons.     

Composition of milk obtained from unmassaged versus massaged breasts of lactating mothers

BACKGROUND: The Oketani method is a program of breast massage and clinical counseling developed by the midwife Satomi Oketani. The purpose of this study is to examine the effects of the method on the quality of breast milk by determining the chemical composition of the milk before and after massage. METHODS: Milk samples were obtained immediately before and after massage from healthy, exclusively breast-feeding Japanese mothers at two different periods of lactation one <3 months the other >3 months after parturition. Lipids, whey protein, casein, lactose, ash, and total solids in milk were measured in milk samples. The gross energy content of milk was estimated. RESULTS: Breast massage significantly increased lipids in the late lactating period but not in the early lactating period. In the early lactating period casein was increased by breast massage but was not significantly affected in the late lactating period. Breast massage caused a significant increase in total solids from the first day to 11 months post partum. The gross energy in the late lactating period was significantly increased by breast massage but not in the early lactating period. Lactose was not significantly changed by breast massage. CONCLUSIONS: Breast massage improves the quality of human milk by significantly increasing total solids, lipids, and casein concentration and gross energy. The milk of mothers treated by Oketani breast massage may improve the growth and development of infants.     

Cerebral hemodynamics and metabolism in adult moyamoya disease: Comparison of angiographic collateral circulation

PURPOSE: The extent of the hemodynamic and metabolic impairments in adult patients with moyamoya disease is still controversial. The aim of the present study was to evaluate the hemodynamic and metabolic status in relation to the development of basal moyamoya vessels (BMVs). METHODS: The cerebral blood flow (CBF), cerebral metabolic rate of oxygen (CMRO2), oxygen extraction fraction (OEF), and cerebral blood volume (CBV) were measured using PET in ten patients with ischemic adult moyamoya disease (mean age, 36.6 years) and six age-matched normal controls (mean age, 33.3 years). The cerebrovascular reserve (CVR) after acetazolamide (ACZ) loading was also estimated using iodine-123 N-isopropyl-p-iodo amphetamine single photon emission computed tomography (123I-IMP SPECT). RESULTS: Based on the angiographic findings, eleven cerebral hemispheres with well-developed BMV (extensive BMV hemispheres) and nine cerebral hemispheres with diminished BMV (diminished BMV hemispheres) were identified. The main routes of collateral circulation in extensive BMV hemispheres were BMVs and leptomeningeal anastomoses. On the other hand, in diminished BMV hemispheres, transdural anastomosis was predominant, and leptomeningeal anastomoses were less developed. In cortices distal to the occluded internal carotid artery, the extensive BMV hemispheres exhibited a significantly lower CBF, CMRO2, CBF/CBV, and CVR (p < 0.05) and a significantly higher CBV and OEF than in diminished BMV hemispheres and controls (p < 0.05). Except for the CBF in the white matter, the mean hemodynamic and metabolic parameters of the diminished BMV hemispheres were not significantly different from those of the controls. CONCLUSION: The extensive development of basal moyamoya vessels is a sign of severe hemodynamic impairment in adult patients with ischemic moyamoya disease. The results may not apply to adults with hemorrhagic onset.     

Cortical activation shortly after cochlear implantation

We evaluated the cortical activations in postlingually deaf cochlear implant (CI) users in the early period (0-2 months) of CI usage. The subjects were 8 early CI users and 8 normal subjects. With tone burst stimuli (1 kHz) delivered to the right side, strong and broad activation of the ipsilateral (right) primary auditory cortex with 2 peaks and weaker activation of the contralateral (left) temporal lobe were observed in early CI users, in a clear contrast with the normal subjects in whom activation was observed in a small area of the contralateral (left) primary cortex. With word stimuli, activation of the superior frontomedian cortex presumably including the supplementary motor area and the neighboring cingulate gyri was observed in early CI users, which was absent in normal subjects. The activation in the immediate association cortices near the primary area was lower in early CI users, while the periphery of the association cortex seemed to be more mobilized.