Detection of needle puncture to blood vessel using puncture force measurement.

Although blood sampling is frequently performed, a system to take blood samples automatically has not yet been developed. In the paper, as a first step towards automatic blood sampling, an examination of an automatic method for puncturing blood vessels is described. The force waveforms produced by puncturing rabbit ear veins were measured. A characteristic peak, possibly associated with the needle piercing the vessel wall, was observed in each waveform of ten successful cases of 14 trials. An algorithm that allowed the detection of this peak was developed, and parameters of a filter to improve the accuracy of the algorithm were determined. Using this algorithm, automatic needle punctures were performed in a rabbit ear vein and then were simulated using the data derived from manual needle puncture on four other rabbits. The results gave 30 fully successful cases of 33 trials of needle puncture and showed that measurement of the puncture force may be important for automatic needle puncture of blood vessels.

Albumin thiolate anion is an intermediate in the formation of albumin-S-S-homocysteine.

An elevated concentration of plasma total homocysteine is an independent risk factor for cardiovascular disease. Greater than 80% of circulating homocysteine is covalently bound to plasma protein by disulfide bonds. It is known that albumin combines with cysteine in circulation to form albumin-Cys(34)-S-S-Cys. Studies are now presented to show that the formation of albumin-bound homocysteine proceeds through the generation of an albumin thiolate anion. Incubation of human plasma with l-(35)S-homocysteine results in the association of >90% of the protein-bound (35)S-homocysteine with albumin as shown by nonreduced SDS-polyacrylamide gel electrophoresis. Treatment of the complex with beta-mercaptoethanol results in near quantitative release of the bound l-(35)S-homocysteine, demonstrating that the binding of homocysteine to albumin is through a disulfide bond. Furthermore, using an in vitro model system to study the mechanisms of this disulfide bond formation, we show that homocysteine binds to albumin in two steps. In the first step homocysteine rapidly displaces cysteine from albumin-Cys(34)-S-S-Cys, forming albumin-Cys(34) thiolate anion and homocysteine-cysteine mixed disulfide. In the second step, albumin thiolate anion attacks homocysteine-cysteine mixed disulfide to yield primarily albumin-Cys(34)-S-S-Hcy and to a much lesser extent albumin-Cys(34)-S-S-Cys. The results clearly suggest that when reduced homocysteine enters circulation, it attacks albumin-Cys(34)-S-S-Cys to form albumin-Cys(34) thiolate anion, which in turn, reacts with homocysteine-cysteine mixed disulfide or homocystine to form albumin-bound homocysteine.

Combined use of electrosurgical incisions and balloon dilatation for the treatment of refractory postoperative pyloric stenosis.

BACKGROUND: Drug therapy plus balloon dilatation without gastroscopic incision does not always relieve postoperative pyloric stenosis. METHODS: Five patients with postoperative pyloric stenosis whose symptoms did not improve with drug therapy and balloon dilatation underwent a combination of gastroscopic incision and balloon dilatation. Two or 3 small radial incisions were made in the stenotic muscle of the pylorus electrosurgically at gastroscopy. Then the stenotic muscle layer was loosened and split bluntly along the incisions with balloon dilatation for 15 to 20 minutes. One week later, the combination procedure or balloon dilatation alone was repeated to prevent restenosis. RESULTS: In the 5 patients, the stenosis was improved with the combination therapy. No complications were observed. CONCLUSIONS: Combined use of gastroscopic incision and balloon dilatation may be considered for patients with refractory pyloric stenosis caused by surgical truncal vagotomy.

Observation of skin thermal inertia distribution during reactive hyperaemia using a single-hood measurement system.

An attempt was made to image the thermal inertia (defined as the square root of the product of thermal conductivity, specific heat and density) of the skin to observe the distribution of blood in the skin during post-occlusive reactive hyperaemia in normal healthy volunteers. The method was based on the ability to calculate thermal inertia by successive thermographic measurements of the skin after stepwise change in ambient radiation temperature surrounding the skin area. The stepwise change was achieved within 0.1 s through a single hood. Experimentation on the undisturbed volar forearm of normal subjects at the same site showed that the measurements thus achieved were reproducible. The thermal inertia values of forearm skin in normal subjects were scattered throughout the range 1.1 x 10(3) to 1.7 x 10(3) W s(1/2) m(-2) K(-1). Experiments on forearm skin subjected to arterial cuff occlusion indicated that thermal inertia can be detected at a low level of blood perfusion. A linear relationship was observed between thermal inertia and blood perfusion measured by laser Doppler imager before and during blood flow occlusion. During reactive hyperaemia, the thermal inertia image exhibited a non-uniform island-shaped pattern of distribution over the forearm, suggesting that, after release from occlusion, recovery of blood flow is non-uniform.

Structural analysis of gene encoding cuticle protein BMCP18, and characterization of its putative transcription factor in the silkworm, Bombyx mori.

BMCP18(2) is one of the major cuticle proteins identified in the larval cuticle of the silkworm, Bombyx mori. A genomic clone coding for BMCP18 was isolated from a B. mori genomic library, and its structure was analyzed. The BMCP18 gene consists of three exons interspersed by two introns. Bm1 element-like sequences were identified around this gene, suggesting possible involvement of this retroposon in the duplication of B. mori cuticle protein genes during evolution. A structural comparison of the BMCP18 gene and related cuticle protein genes of other lepidopteran species (MSCP14.6 and HCCP12) showed that the 5' upstream region of the BMCP18, MSCP14.6, and HCCP12 genes has a 12-bp identical sequence matching the recognition sequence for transcription factors COUP-TF and HNF-4. This implies that molecular mechanisms regulating expression of these cuticle protein genes are also conserved. mRNAs coding for Bmsvp, the B. mori homolog of Drosophila Seven-up, which is known as a homolog of vertebrate COUP-TF, and BmHNF-4, a homolog of vertebrate HNF-4, were detected in the larval epidermis. Bmsvp bound to the 12-bp sequence in vitro, suggesting that Bmsvp regulates the BMCP18 gene expression.

Continuous monitoring of single-sweat-gland activity.

A conductivity measurement system using a small ion-free-solution perfusion chamber has been developed to monitor single sweat-gland activity (SSGA) continuously at the skin surface. The chamber has a small open space of 0.2 mm2 at the bottom and has a transparent window. Single sweat pores were visualized by the starch/iodine method and the chamber was attached onto a single sweat pore using a magnifying lens affixed at the window. Silver electrodes were installed inside the chamber, and, by perfusing ion-free solution through the chamber at a constant flow rate, the conductivity of the solution was measured at the inlet and the outlet of the chamber. Continuous SSGA was monitored at the palm, finger tip and chest skin surface when the subjects were seated in a resting position and under stresses such as hand grasping with a dynamometer and performing mental arithmetic. Different types of response were observed from different sweat pores. The response time of this system was less than 0.15 s. The present results reveal that continuous sweat activity can be monitored even from a single sweat gland.

Continuous estimation of systolic blood pressure using the pulse arrival time and intermittent calibration.

A continuous noninvasive method of systolic blood pressure estimation is described. Systolic blood pressure is estimated by combining two separately obtained components: a higher frequency component obtained by extracting a specific frequency band of pulse arrival time and a lower frequency component obtained from the intermittently acquired systolic blood pressure measurements with an auscultatory or oscillometric system. The pulse arrival time was determined by the time interval from QRS apex in electrocardiogram to the onset of photoplethysmogram in a fingertip beat-by-beat via an oximetric sensor. The method was examined in 20 patients during cardiovascular surgery. The estimated values of systolic blood pressure were compared with those measured invasively using a radial arterial catheter. The results showed that the correlation coefficients between estimated values and invasively obtained systolic blood pressure reached 0.97 +/- 0.02 (mean +/- SD), and the error remained within +/- 10% in 97.8% of the monitoring period. By using a system with automatic cuff inflation and deflation to acquire intermittent systolic blood pressure values, this method can be applicable for the continuous noninvasive monitoring of systolic blood pressure.

Mechanisms for the formation of protein-bound homocysteine in human plasma.

Hyperhomocysteinemia is an independent risk factor for cardiovascular disease. Greater than 70% of homocysteine in circulation is protein-bound. An in vitro model system using human plasma has been developed to study mechanisms of protein-bound homocysteine formation and establish the equilibrium binding capacities of plasma for homocysteine. Addition of homocysteine to plasma caused an initial rapid displacement of cysteine and a subsequent increase in protein-bound homocysteine. This rapid reaction was followed by a slower oxygen-dependent reaction forming additional protein-bound homocysteine. To determine the equilibrium binding capacity of plasma proteins for homocysteine, plasma was treated with 0.5-10 mM dl-homocysteine for 4 h at 37 degrees C under aerobic conditions. Under these conditions the equilibrium binding capacity was 4.88 +/- 0.51 and 4.74 +/- 0.68 micromol/g protein for male (n = 10) and female (n = 10) donors, respectively. The mechanism of protein-bound homocysteine formation involves both thiol-disulfide exchange and thiol oxidation reactions. We conclude that plasma proteins have a high capacity for binding homocysteine in vitro.

Classification of waist-acceleration signals in a continuous walking record.

We attempted to distinguish walking on level ground from walking on a stairway using waist acceleration signals. A triaxial accelerometer was fixed to the subject's waist and the three acceleration signals were recorded by a portable data logger at a sampling rate of 256 Hz. Twenty healthy male subjects were asked to walk through a corridor and up and down a stairway as a single sequence, without any instruction. The data were analyzed using discrete wavelet transform. Walking patterns were classified in two stages. In the first stage, the times when the walking pattern changed were detected using the low-frequency component of the anteroposterior acceleration (LF(A)) and of the vertical acceleration (LF(V)). In the second stage, the three types of walking patterns were classified by comparing powers of wavelet coefficients in the vertical direction (P(WCV)) and in the anteroposterior direction (RP(WCA)). Changes in walking patterns could be detected by using either LF(A) or LF(V). Walking down stairs could be distinguished from the other types of walking as it gave the largest value in P(WCV), and walking up stairs could be discriminated from level walking using RP(WCA). Level and stairway walking could be classified from continuous records of waist acceleration.

Analysis of acceleration signals using wavelet transform.

In this study, we attempted to discriminate the acceleration signal for horizontal level and stairway walking using wavelet-based fractal analysis method. The acceleration signal was measured close to the center of gravity of the body, while the subjects walked continuously in the corridor and up and down the stairs. We used the wavelet-based fractal analysis method to discriminate walking pattern. The parameter H which is related directly to the fractal dimension was estimated by the wavelet coefficient and was changed into low value during walking upstairs. By manually setting the threshold level for individual, it was possible to discriminate walking upstairs from the other walking type. However, the common feature among subjects was not shown between level walking and walking downstairs.

Preliminary study of continuous glucose monitoring with a microdialysis technique and a null method--a numerical analysis.

Monitoring of the subcutaneous tissue glucose concentration is an attractive method for continuous monitoring of the glucose concentration in diabetic patients. Several researchers have studied this, but no satisfactory method has been developed. We have proposed a new method, which can measure the glucose concentration of subcutaneous tissue continuously, even as the efficiency of membrane perfusion and sensor performance decline. Two reference solutions were prepared with concentrations higher and lower than the objective solution. They were perfused alternately for different ratios of perfusion times. The glucose concentration, after perfusing microdialysis, was detected and the trend of changes in the concentration was used to control the ratio of the two perfusion solutions. When the trend was a unity, the glucose concentration was calculated from the ratio of the two perfusion solutions. The numerical study was performed with a compartment model and a basic control theory. In simulation, the 90% response time to step change was approximately 7 min, which is fast enough when compared with the fluctuation of glucose in the electrolyte. This result suggested that this new system might be useful for continuous monitoring of the glucose concentration in subcutaneous tissue.

Intraperitoneal injection of dextran sulfate as an anti-adherent drug for the prevention of peritoneal metastasis of cancer shows low toxicity in animals.

Intraperitoneal dextran sulfate with a mean molecular weight of 5 x 10(5) has been developed for use in an anti-adherent therapy against peritoneal carcinomatosis. The present study examined acute toxicity of i.p. injection of dextran sulfate in mice and rabbits. The 10, 50 and 90% lethal dose values are 0.213 (0.146-0.252), 0.336 (0.291-0.405) and 0.530 mg/g (0.431-0.873 mg/g: 95% confidence interval) in mice, respectively. These are markedly larger than the efficacious dose of 0.005-0.01 mg/g obtained previously. Death or symptoms of intoxication were seen within 3 days after administration of toxic doses. Rabbits received i.p. injection of dextran sulfate at 0.02 mg/g, which was close to the efficacious dose. At 2, 4, 6, 8 and 13 days after administration, blood was taken for biochemical and hematological analyses. Dextran sulfate at 0.02 mg/g induced no remarkable abnormal findings. These results suggest that the i.p. dextran sulfate is safe as an anti-adherent agent against peritoneal metastasis of cancer.

[Influence of the radioactive strontium (89Sr) using for nuclear medical radiation therapy upon radioactive draining-water system].

PURPOSE: Strontium-89 chloride (89Sr) is a new radiopharmaceutical that provides effective pain relief for metastatic bone lesions, and is expected to be available soon in the palliative management for metastatic bone pain in Japan. Because of relatively long physical half life (50.5 days), 89Sr may affect to the radioactive draining-water system by exceeding the limits of activity concentration for radioactive drain. In this article, the influence of 89Sr use on the radioactive drainage system was simulated. METHODS: The standard tank capacity of drainage and draining frequency was determined from the results of questionnaire carried out for the nationwide medical and research institutes where radioisotope treatment are performed. On the assumption that 89Sr of 148 MBq for one therapy was used twice a week and several common radionuclides were used as the same activity as used at Chiba Cancer Center, the influence of 89Sr was estimated. The calculation was performed using the activity contamination ration into the draining-water system of each radionuclide of 0.01, which was legally determined. RESULTS: The simulation revealed that the sum of the contamination ratios of individual radionuclides exceeded a legal value of 1.0 in standard drainage with the capacity of 5 m3 and 10 m3 and draining frequency of 7 times per year. The actual contamination ratios of common radiopharmaceuticals measured at Chiba Cancer Center ranged from 1/100 to 1/1000 of the legal values. CONCLUSION: It is necessary that the legal value of activity contamination ratios into the draining-water system should be reassessed before starting 89Sr therapy.

Dextran sulfate inhibits injured abdominal wall-specific tumor implantation in mice.

Tumor recurrence is often seen at sites where the peritoneum has been injured during surgery for gastrointestinal malignancies. It is thought that malignant cells released from the tumor during surgery implant in the sites of injury in the abdominal wall and cause tumor recurrence. Here we use dextran sulfate (DS) as an antagonist to cell adhesion for preventing implantation of i.p. seeded malignant cells, thus suppressing the recurrent tumor formation often observed at the site of injury in postoperative abdominal walls. DS was tested for anti-adherent activity against B-16 melanoma cells to injured abdominal wall specimens ex vivo and showed the capacity to significantly impair B-16 melanoma cell adherence compared to controls without DS. DS was also tested for the activity to prevent i.p. seeded B-16 melanoma cells from implanting in the site of injury in the abdominal wall in vivo and DS prevented B-16 melanoma cells from implanting in the sites of injury in the abdominal wall. In the test for the activity to improve survival in mice after B-16 melanoma was inoculated i.p., DS improved the survival of mice as compared to the controls without DS. We conclude that DS may be useful in preventing surgically promoting tumor implantation at sites of injury in post-operative abdominal wall treated for gastrointestinal malignancies.

Chronodiagnostic acquisition of recovery speed of heart rate under bathing stress.

Cycling on an ergometer is one effective means of measuring cardiovascular function while applying stress on the heart. Bathing in a hot water bath applies a low stress to the heart. The electrocardiograms of a healthy adult male (aged 35 at the start of study) were recorded while taking a hot water bath with no electrode attached to the body over a period of 2 years (376 days over a 762 day period). The recovery speed following the initial overshoot of the heart rate (HR) was observed. The bathtub was designed for the automatic acquisition of ECG data. Immediately after immersion in the tub, the HR reached a peak within 20 s and then exponentially decreased toward the lowest rate in the 120 s of bathing. The initial recovery speed of the HR from the stress of bathing had a specific rhythm in the subject. Spectrum analysis of the speed series indicated that slow recovery speed appeared in cyclic periods of approximately 1 year, 42 days and 17 days. The methodology may provide a chronodiagnostic index of an exercise test for cardiovascular function.

Evaluation of the therapeutic effect of radiotherapy on cervical cancer using magnetic resonance imaging.

PURPOSE: This study was performed to evaluate magnetic resonance imaging (MRI) in determining the therapeutic effect of radiotherapy (RT) on cervical cancer. METHODS AND MATERIALS: Serial MRI studies were performed in 42 patients with predominantly advanced cervical cancer before, during, and after radiotherapy. Patients underwent external irradiation combined with high-dose-rate intracavitary (HDR) brachytherapy. T-2 weighted spin-echo pulse sequences with long repetition and echo times were used at a field strength of 1.5 T. Multiple punch biopsies of the cervix were obtained from the high-signal intensity area in all patients at the same time as the MRI. RESULT: In biopsies performed immediately after RT, no residual tumors were found in 36 patients (86%); in 6 patients, residual tumors were observed. The simultaneous MRI study demonstrated no high-signal intensity on T2-weighted images in 28 patients. A high-signal area was observed in 14 patients, and this disappeared 3 months after RT in 8 patients with a negative histological study. The sensitivity, specificity, and accuracy of MRI studies at 3 months after RT were 100%. When the relationship between reduction of tumor volume at 30 Gy and local tumor control was analyzed, every patient with a reduction under 30% gained local control. Also, patients with no residual tumors 3 months after RT gained local control. CONCLUSION: MRI studies performed at 30 Gy of external irradiation and 3 months after RT were predictive factors of local control.

Extensive gastrectomy and carbon-adsorbed mitomycin C for gastric cancer with peritoneal metastases. Case reports of survivors and their implications.

BACKGROUND/AIMS: Extensive gastrectomy, defined as gastrectomy with complete omentectomy and extended lymphadenectomy, improves the survival of gastric cancer patients with peritoneal metastases, even though peritoneal metastasis is considered the end-stage of cancer. MMC-CH, a new dosage formulation of mitomycin C, extended the survival of rabbits with peritoneal carcinomatosis as compared to aqueous mitomycin C. METHODOLOGY: We retrospectively reviewed 114 patients who underwent gastrectomy for gastric cancer with peritoneal metastases. RESULTS: Six patients survived for more than 5 years after the therapy out of 63 patients treated with MMC-CH therapy and extensive gastrectomy for gastric cancer with P1, i.e., metastases to the adjacent peritoneum but no metastasis to the distant peritoneum, or P2, i.e., a few metastases to the distant peritoneum. However, there were no 5-year survivors in patients with P3, i.e., numerous metastases to the distant peritoneum, or in patients treated with incomplete omentectomy, limited lymphadenectomy and no MMC-CH therapy. CONCLUSIONS: The results imply that gastric cancer patients with P1 or P2 have a possible chance to survive more than 5 years when treated with MMC-CH therapy and extensive gastrectomy.

Effect of extensive lymph node dissection on the survival of early gastric cancer.

BACKGROUND/AIMS: A retrospective analysis of 628 cases of early gastric cancer was performed to evaluate prognostic significance of extensive lymph node dissection. METHODOLOGY: The patients were assigned to either D0/D1 (n=177) group or D2/D3 group (n=451) according to the extent of lymph node dissection and the survival of the two groups was compared. RESULTS: The survival rate of D2/D3 group was significantly higher than D0/D1 group in the case of both including and excluding unrelated cause of death (p<0.0001 and p<0.005, respectively). CONCLUSIONS: Though early gastric cancer is excellent prognostic disease, very few numbers of patients with recurrence really remain. Our data show extensive lymph node dissection was effective to prolong the survival of patients with early gastric cancer.

[Tumor imaging using 201Tl chloride and 67Ga citrate in nucleomedical surveys].

Among nucleomedical examinations for cancer, tumor imaging using 201Tl chloride and 67Ga citrate can be easily performed at almost any hospital. However, the planar images usually obtained are not sufficient to detect small tumorous lesions. For more accurate detection, tomographic images particularly single photon emission CT (SPECT) is necessary. SPECT is also indispensable in cancer diagnosis. Whether 201Tl SPECT or 67Ga SPECT is chosen depends upon tumor localization, histological type, and the final purpose of the study. 201Tl accumulates in almost all tumors, but it is not suitable for detection of abdominal lesions, because there is much physiological accumulation in the small intestine and kidney. In contrast, 67Ga does not always accumulate in adenocarcinomas. 201Tl SPECT and 67Ga SPECT are more useful in the functional imaging of cancer than is morphological tumor diagnosis. Both methods are useful in monitoring treatment effectiveness, detecting recurrent lesions after surgery and radiotherapy, and predicting the grade of malignancy of the tumor. Tumor SPECT using 201Tl chloride and/or 67Ga citrate provides clinically useful information not obtained by morphological tumor diagnosis only.

67Ga planar imaging with a low-energy collimator and scatter correction using the triple energy window method.

To improve the spatial resolution and contrast of 67Ga planar imaging, we used a low-energy collimator and two lower-energy windows with a triple-energy-window (TEW) scatter compensation method. The spatial resolution is better than with a medium-energy collimator, and the TEW method can correct for scattered photons and reduce the background counts. In a phantom study and a clinical study involving 44 patients, the images obtained by the proposed method were compared with the images obtained with a medium-energy collimator and three energy windows without scatter compensation (the conventional method). The spatial resolution and the counts were measured. Two nuclear medicine physicians interpreted the images and clinical usefulness was evaluated. The spatial resolution and contrast were improved by our proposed method. It enabled the detection of lesions in five locations in the clinical study. The counts were reduced but misreadings were not seen. We conclude that our proposed method shows a clinical advantage over the conventional method. It can be used easily and quickly with commercially available equipment and is useful in clinical practice.