Monitoring of the central blood pressure waveform via a conformal ultrasonic device.

Continuous monitoring of the central-blood-pressure waveform from deeply embedded vessels, such as the carotid artery and jugular vein, has clinical value for the prediction of all-cause cardiovascular mortality. However, existing non-invasive approaches, including photoplethysmography and tonometry, only enable access to the superficial peripheral vasculature. Although current ultrasonic technologies allow non-invasive deep-tissue observation, unstable coupling with the tissue surface resulting from the bulkiness and rigidity of conventional ultrasound probes introduces usability constraints. Here, we describe the design and operation of an ultrasonic device that is conformal to the skin and capable of capturing blood-pressure waveforms at deeply embedded arterial and venous sites. The wearable device is ultrathin (240 μm) and stretchable (with strains up to 60%), and enables the non-invasive, continuous and accurate monitoring of cardiovascular events from multiple body locations, which should facilitate its use in a variety of clinical environments

Preoperative multidisciplinary treatment with hyperthermia for soft tissue sarcoma

We report the results of phase I/II studies of preoperative multidisciplinary treatment of 14 patients with soft tissue sarcoma using hyperthermia from November 1990 to April 1995. The preoperative treatment was conducted with thermo-radio-chemotherapy in 11 cases of stage III, and with thermo-radiotherapy as well as thermo-chemotherapy in three cases of stages I and II. Hyperthermia was carried out twice a week with totals ranging from 4 to 14 times (average: 8.4 times); each session lasted 60min. Radiotherapy was administered four or five times per week, and the dose was 1.8 2Gy/fraction, with a total of 30-40Gy in a four week period. Chemotherapy was mainly in the form of MAID regimen (2-mercaptoethanesulphonic acid (mesna), adriamycin, ifosfamide and dacarbazine). The tumors were surgically resected in all patients after completing the preoperative treatment. The efficacy rate, as expressed by the percentage of either tumors in which reduction rate was 50% or more, or tumors for which post-treatment contrast enhanced CT image revealed low density volumes occupying 50% or more of the total mass, was 71 % (ten of the 14 tumors). The mean tumor necrosis rate in the resected specimens was 78%. The tumor necrosis rate was significantly high (P &#60; 0.05) in patients whose Time &#8805; 42°C was of long duration. Postoperative complications were observed in six patients; among these, two patients developed wound infection that required surgical treatment as a complication of surgery performed in the early stage following the preoperative treatment. After a mean postoperative follow-up of 27 months, distant metastasis occurred in four patients resulting in three fatalities. The three-year cumulative survival rate was 64.3%. No local recurrence was observed in any patient during the follow-up, thus confirming our hypothesis that preoperative multidisciplinary treatment has an excellent local efficacy. We think that it would be valuable to conduct, at many facilities, phase III studies on the treatment of soft tissue sarcoma by a combination of surgery and preoperative multidisciplinary treatment using hyperthermia, paying close attention to the interval between these two modalities.</p

Hyperthermotherapy for postoperative local recurrences of rectal cancer.

Between November 1984 and August 1992 we used hyperthermotherapy in six cases of local recurrence of rectal cancer. Hyperthermotherapy was performed on the average 8.7 times (range: 3-18) for each patient for 60 min each. All patients underwent combined radiotherapy and received a mean radiation dose of 42.5 Gy (range: 9-60 Gy). Five patients underwent heating within 1 h after irradiation and one patient simultaneously with the irradiation. Four patients underwent combined chemotherapy and two patients immunotherapy. Before the treatment all patients had painful lesions, but pain decreased posttherapeutically in five patients. Performance status improved in two patients. High carcinoembryonic antigen levels prior to the therapy in four patients decreased in all cases after treatment. Posttherapeutical computed tomograms revealed only minor response or no changes. After the treatment, four patients died of exacerbations of recurrent tumors and one patient of distant metastases. The patient who underwent simultaneous radiohyperthermotherapy is presently alive, in August 1992, 38 months after initiation of the treatment. The 50% survival time after initiation of the treatment was 25 months (range: 10-38 months). Hyperthermotherapy combined with radiotherapy, chemotherapy and/or immunotherapy was useful for the alleviation of pain in patients who developed local recurrence after surgery, and improved survival after recurrences can be expected.</p

Hyperthermotherapy added to the multidisciplinary therapy for penile cancer.

We performed a long-term follow-up of 4 patients with penile cancer who underwent hyperthermotherapy from August 1985 until August 1992. Hyperthermia was applied using a frequency of 350 MHz with a waveguide applicator twice a week for 60 min each for an average of 9.5 times (varying from 6 to 13 times). The total heating time that the temperature of urethra could be kept above 42 degrees C, was 166 min on the average (ranging from 0 to 463 min). Two patients classified as stage I according to the Jackson classification and 1 patient classified as stage IV underwent combined radiotherapy and received an average radiation dose of 53 Gy (range, 40-70 Gy). Among these patients 2 underwent combined chemotherapy with bleomycin or peplomycin. Malignant cells disappeared posttherapeutically and in August 1992, after an average of 5 years and 9 months (varying from 4 years 6 months to 6 years 10 months), the patients were free of recurrences. The one patient on stage IV had extensive invasion of the abdominal wall, but still recovered completely. One patient on stage III underwent combined chemotherapy and hyperthermotherapy, but heating had obviously been insufficient. There was a residue of malignant cells after the treatment and we performed a penectomy. Regarding functional preservation of the penis a multidisciplinary therapy incorporating hyperthermotherapy can be expected to increase the curativity. This indicates that it could induce in an advanced case, where an operation would be difficult, complete remission.</p

Immunofluorescent Studies on Viral Antigens of the Mammary Cancer in C(3)H Mice. Ⅰ. Purification Study of Viral Antigens in C(3)H Mouse Mammary Cancer and its Evaluation by Direct Immunofluorescent Staining

Virus preparations were obtained from mammary tumors which developed spontaneously in C(3)H mice by three different methods; 1) filtration through Berkefeld-N or Chamberland L(3) filters, 2) differential centrifugations, and 3) fluorocarbou extraction. Each virus preparation was used for immunizing rabbits, and was then evaluated for the degree of purification of the viral antigens by direct immunofluorescent staining. Following results were obtained: 1. The fluorocarbon extractin method was more excellent for the purification of mammary cancer virus than filtration or differential centrifugation method. 2. Staining procedure of the direct immunofluorescence was improved as follows; frozen sections were fixed with cold acetone-fluorocarbon mixture instead of coid acetone, and duration of staining was prolongel over six hours in a cold moist chamber. As a result it was possible to observe clearer and more numerous fluorescence than by the direct staining of Coons' original procedure

Immunofluorescent Studies on viral Antigens of the Mammary Cancer in C(3)H Mice. Ⅱ. Demonstration of Viral Antigens in C(3)H Mouse Mammary Cancer as Studied with Anti-Complementary Fluorescent Serum

As mentioned in the author's previous study, the complement method of immunofluorescence allowed to observe clearer fluorescence of the viral antigen than by the direct and indirect method. In this study, therefore, localizaton of viral antigens of C(3)H mammary cancer was persued with the fluorescescent serum that reacted immunologically with the complement. 1. The viral antigen was observed in tumor cells and intercellular spaces and particularly rich in perivascular portions. 2. In the metastastatic lymph nodes viral antigens were observed in some tumor cells, and in the spleen of tumorbearing mice they were observed within retculum cells on rare ocasions. 3. Intracellular localization of viral antigens was spread in the peripheral portions of the cytoplasm of tumor cells, and no specific fluorescence was observed in the nucleus of tumor cells. 4. No specific fluorescence was seen in the liver, kidney, lung, bone marrow and brain of the tumor-bearing C(3)H mice and in tissues of normal mice. 5. In mice with spontaneous mammary cancer, viral antigens were encounted more frequently than in mice with transplanted tumors

Studies On the Effects of Cytochrome C On the Hematopoiesis of Bone Marrow Part 2 Effects of Cytochrome C On Leukopoietic Functions By Means of Bone Marrow Tissue Cuiture Supplement: Clinical Application of Cytochrome C to Some Hematological Disorder

By means of bone marrow tissue culture the author investigated the effects of cytochrome C on leukopoietic function and obtained the following results: 1) When cytochrome C was added directly to the bone marrow tissue culture of normal guinea pigs, normal persons and patients with various diseases the growthrate of outgrowth, the wandering velocity and carbon particle phagocytosis of neutrophils were increased as compared with those of the control added with saline. As the result, it has been seen that by adding an optimal amount of cytochrome C the leukopoietic functions of bone marrow were accelerated. 2) When cytochrome C was added with carcinostatic substances to the bone marrow tissue culture of normal persons, the growth rate of outgrowth, the wandering velocity and the carbon-particle phagocytosis of neutrophils were increased as compared with those of the control added with only carcinostatic substances. The similar results were obtained in the case of bone marrow tissue culture of guinea pigs of which bone marrow had been made hypoplastic by repeated administration of carcinostatic substauces and then injected with the repeated administration of cytochrome C. On the other hand, in its clinical applications, the repeated administration of cytochrome C were effective on some cases of leukopenia induced with carcinostatic substances. As it has been demonstrated that cytochrome C has some relieviug effects on the disturbance of leukopoietic functions of bone marrow successively injected with carcinostatic substances

Studies on Lipoprotein Lipase Ⅱ. Changes in Endogenous Lipoprotein Lipase Activity and Lipids of Man and Rabbit Plasma in Oral Glucose Tolerance Test

The previous finding noted in man of significant difference in endogenous lipoprotein lipase (ELPL) activity of plasma in oral glucose tolerance test (OGTT) between diabetic state and non-diabetic state has been confirmed and attested by experiments in rabbits. Observations were also made of plasma lipid changes associated with OGTT and of those in rabbits with developing steroid-diabetes by corticosteroid injection, with the results as follows. 1) In OGTT, non-diabetic state exhibited a bi-peaked curve for plasma ELPL activity with maxima at 90 and 150 minutes after an oral dose of glucose whereas diabetic state showed an activity curve with a single peak at 90 minutes after oral glucose administration. 2) In OGTT, non-diabetic rabbits (maintained on bean-curd refuse diet or lanolin diet) exhibited a bi-peaked curve for plasma ELPL activity with maxima at 30 and 120 minutes after an oral dose of glucose whereas rabbits with alloxan-or steroid-diabetes showed an activity curve with a single peak at 90 minutes after oral glucose administration. 3) During the OGTT the animals displayed prominent changes in plasma nonesterified fatty acid levels while such other plasma lipid factors as triglycerides, total cholesterol, phospholipid and total lipid remained virtually unchanged. 4) Steroid-induced diabetes was faster in onset in lanolin fed rabbits with hyperlipidemia, compared with animals maintained on bean-curd refuse diet. 5) The most prominent feature of abnormal lipid metabolism observed in rabbits with developing steroid-diabetes was elevation of serum triglycerides. 6) Principal fatty acid levels in the plasma of rabbits receiving a corticosteroid were determined at certain time-intervals during the OGTT. All these fatty acids showed changes with time, being particularly marked at 180 minutes after glucose administration; changes of palmitic acid, oleic acid and linoleic acid concentrations were conspicuous in both the bean-curd refuse fed group and the lanolin fed group

Studies On the Effects of Cytochrome C On the Hematopoiesis of Bone Marrow Part 1 Effects of Cytochrome C On the Thrombopoietic Function By Means of Bone Marrow Tissue Culture

By means of bone marrow tissue culture method deviced by Hiraki, the author investigated the effects cytochrome C on the thrombopoietic function in bone marrow and obtained the following results. 1) Cytochrome C diluted in several concentrations was added to the bone marrow tissue culture of normal guinea pigs, normal persons and patients with various diseases. Average number of megakaryocytes in the growth zone and its thrombopoietic function were examined. As a result, it has been seen that the thrombopoietic functions of normal bone marrow added with an optimal amount of cytochrome C were moderately accelerated both in guinea pigs and human beings as compared with that of control added with saline. 2) The cytochrome C and each of three kinds of carcinostatic substances; mitomycin C, trenimon, and carzinophyllin were added to the bone marrow tissue culture of normal persons the effects of these drugs on the thrombopoietic functions in the bone marrow were investigated. On the other hand, the bone marrow of guinea pigs of which bone marrow had been rendered to hypoplastic by repeated administration of the above described carcinostatic substances and then treated with repeated administration of cytochrome C were cultured. The thrombopoietic functions of megakaryocytes in these bone marrow tissue culture treated with cytochrome C were maintained moderately high as compared with the control treated with carcinostatic substances and saline only. From these results it could be concluded that cytochrome C has the accelerating effects on the thrombopoietic function of normal bone marrow as well as the protecting effects on the thrombopoiesis from the myelodegenerative especially thrombopoiesisinhibiting action of several carcinostatic substances