Hyperfine-interaction constants of the 8D3/2 state in 85Rb using quantum-beat spectroscopy.
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Journal Article↗
Biomedical subjects
J Koh
Publications and source records attributed to J Koh.
Important influence of respiration on human R-R interval power spectra is largely ignored.
Frequency-domain analyses of R-R intervals are used widely to estimate levels of autonomic neural traffic to the human heart. Because respiration modulates autonomic activity, we determined for nine healthy subjects the influence of breathing frequency and tidal volume on R-R interval power spectra (fast-Fourier transform method). We also surveyed published literature to determine current practices in this burgeoning field of scientific inquiry. Supine subjects breathed at rates of 6, 7.5, 10, 15, 17.1, 20, and 24 breaths/min and with nominal tidal volumes of 1,000 and 1,500 ml. R-R interval power at respiratory and low (0.06-0.14 Hz) frequencies declined significantly as breathing frequency increased. R-R interval power at respiratory frequencies was significantly greater at a tidal volume of 1,500 than 1,000 ml. Neither breathing frequency nor tidal volume influenced average R-R intervals significantly. Our review of studies reporting human R-R interval power spectra showed that 51% of the studies controlled respiratory rate, 11% controlled tidal volume, and 11% controlled both respiratory rate and tidal volume. The major implications of our analyses are that breathing parameters strongly influence low-frequency as well as respiratory frequency R-R interval power spectra and that this influence is largely ignored in published research.
Adult↗
Glue sniffing deaths in Singapore--volatile aromatic hydrocarbons in post-mortem blood by headspace gas chromatography.
Over a period from 1983 to 1991, of a total of 19,000 post-mortems, 33 were found to have at least one aromatic hydrocarbon (benzene, toluene or xylenes) in the blood. Of the 33 deceased, 22 had a history of toluene or petrol abuse while most of the remaining 11 were suspected to be glue sniffers through evidence found at the scene. This number, which represented 0.17 per cent of all the unnatural deaths, is considered small for a nation having a glue sniffing epidemic. The low death rate, as compared to 2.1 per cent through drug and chemical poisoning during the same period, is attributed to the timely intervention by the Government who outlawed glue sniffing and the effectiveness of compulsory rehabilitation. The male gender predominates (81.8 per cent) among the 33 deceased with a mean age of 20.1 years (range 15 to 33). The mean age for the female gender is 17.7 years (range 16 to 20). The blood toluene levels were found to be in the range 0.2 to 92 micrograms per ml blood. The causes of death are: 63.6 per cent due to falling or suicide by jumping; 18.2 per cent drowning; 6.1 per cent hanging; 6.1 per cent homicide; and 6.1 per cent acute toluene poisoning. The high proportion of traumatic deaths are discussed. Headspace gas chromatography with a suitable GC column was used for the analysis. Calibration blood standards were prepared in situ or in bulk stabilized by 10 per cent (v/v) methanol to overcome the hydrophobic and volatile nature of the aromatic hydrocarbons.(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
[Transcatheter arterial chemoembolization to hepatic metastases from colorectal cancer].
Response of transcatheter arterial chemoembolization (TAE) and transcatheter arterial infusion chemotherapy to hepatic metastases was reported in 25 cases of colorectal cancer. The severity of liver metastases was H1 in 12 cases, H2 in 9 cases, and H3 in 4 cases. Liver metastases were found during surgery in 12 of these patients, and 13 showed metastases or recurrence in the liver after resections of primary lesions. Catheters were inserted selectively to the proper hepatic artery by Seldinger's method, followed by injection of embolizing agents (gelfoam particles of Lipiodol) with adriamycin or 5-FU + leucovorin in most cases. Response was assessed by blood CEA levels, diagnostic imaging, and period of survival. In 5 cases in whom liver resections were performed following TAE, response was assessed by histopathological findings of the resected specimens. Two patients showed partial response (PR), 12 no change (NC) and 11 progressive disease (PD) by diagnostic imaging. Blood CEA levels fell to less than 50% of pre-treatment levels in 26% of cases. Histological changes by TAE were confirmed in 4 of 5 cases after liver resections, but viable cancer cells were observed in all cases. A case of mucinous cancer showed no change histologically. As the other case of mucinous cancer showed PD by diagnostic imaging, TAE was not suggested to be suitable to treat cases of mucinous cancer. More improvements in the dosage, drugs and times of treatment were suggested to yield a better response rate in TAE therapy for liver metastases from colorectal cancer.
Adult↗
Antitumor effect of triphenylethylene derivative (TAT-59) against human breast carcinoma xenografts in nude mice.
The antitumor activity of a newly synthesized triphenylethylene derivative [(E)-4-[1-[4-[2-(dimethylamino)ethoxy-phenyl]-2-(4-isopropyl)phenyl-1- butenyl] phenyl monophosphate] (TAT-59) was investigated against human breast carcinoma xenografts in nude mice with reference to the changes of hormone receptors. Five strains (MCF-7, Br-10, R-27, ZR-75-1, and T-61) used for the experiments possessed cytosol estrogen receptor (ER), and their growth was estradiol dependent. Five mg of TAT-59 and tamoxifen citrate (TAM) per kg were administered p.o. daily except Sunday. TAT-59 showed a positive antitumor effect against MCF-7 and R-27, whereas TAM was effective on MCF-7, and their adverse effects detected by mortality rate, body weight loss, and spleen weight loss were similar to each other. The reduction of ER and production of progesterone receptor (PgR) after the treatment with TAT-59 were more potent than after TAM, suggesting that TAT-59 exerts its antitumor effect through binding to ER. These findings suggest that TAT-59 might merit use in clinical trials with breast cancers.
Animals↗
[A case of advanced breast cancer responding to low-dose 5'-DFUR].
A 69-year-old female patient with locally advanced breast cancer with multiple bone metastases (T4cN2-M1) was treated with 5'-DFUR after failure of tamoxifen treatment. The 5'-DFUR dose was limited to 600 mg per day, half the usual dose, because of its gastroenterological side effects. The primary tumor and metastatic axillary lymph nodes regressed three months after the start of treatment, and the complete remission of lesions was obtained in 16 months. Reduction of bone metastasis was confirmed by the disappearance of osteolytic lesion in the skull roentgenogram and the decrease of abnormal accumulation on the bone scintigram. Serum levels of CEA and ST-439 markedly reduced during the treatment as the disease regressed.
Aged↗
[Intra-arterial chemotherapy of local recurrence and non-curative case of colorectal cancer].
Twelve colorectal cancer patients, including 9 with local recurrent cancer and 3 with remnant cancer after surgery, were treated with intraarterial chemotherapy. Three cases were treated with MMC injection alone, 1 case with MMC combined with irradiation (MMC-R) and 8 cases with ADM combined with irradiation (ADM-R). In 7 evaluable patients, the response rate was 28.6% with 1 CR case, 1 PR case and 5 NC cases. The 2 cases treated with ADM-R were successful. Six of 8 patients treated with ADM-R survived more than 1 year, while all 4 patients treated with MMC or MMC-R died within 8 months. The cumulative survival rate after ADM-R treatment was 44% at 24 months. It is suggested that the combination of intra-arterial chemotherapy and radiation therapy is an effective treatment for local recurrence and non-curative cases of colorectal cancer.
Chemotherapy, Adjuvant↗
[A case report of anesthetic management of orthotopic liver transplantation from a living donor to his son].
In November 1989, transplantation of a liver graft from a living related donor was performed at Shimane Medical University Hospital. The donor was a 26-year-old man and the recipient his 1-year-old son. The child had been in end stage of liver cirrhosis. Before the surgery, he required intensive care because of massive bleeding from varices. Anesthesia of the recipient was rapidly induced with ketamine and the trachea was intubated with succinylcholine using cricoid pressure. Anesthesia was maintained with enflurane, fentanyl and pancuronium. Nitrous oxide was used only in the preanhepatic period. Total surgical time and anesthetic time were 945 min and 1065 min, respectively. Total estimated blood loss was 3650 ml and 2780 ml of fresh whole blood was transfused. Careful attention was paid to body temperature, serum potassium, ionized calcium and blood coagulation function, as well as to general cardiovascular and respiratory functions. During anhepatic period, the inferior caval vein was not clamped. Hemodynamic function was relatively stable throughout the operation. At the time of reperfusion of the transplanted graft, there was little change in serum potassium levels or other parameters. Postoperative mechanical ventilation was required for 8 days.
Adult↗
[Experimental combined chemo- and endocrine therapy with UFT and tamoxifen in human breast carcinoma xenografts serially transplanted into nude mice].
We have investigated the experimental combined chemo- and endocrine therapy of UFT and tamoxifen (TAM) on two human breast carcinoma xenografts, R-27 and Br-10 with estrogen receptors (ER) serially transplanted into nude mice. When sc inoculated tumor started the exponential growth, the treatments were initiated in four groups which were control, UFT 20 mg/kg (as tegafur) po daily for 18 times, TAM 5 mg/kg im twice a week for 6 times and UFT + TAM groups. The antitumor activity of the agents were assessed by the growth curves, the lowest T/C ratios of the relative mean tumor weight and the actual tumor weights at the end of the experiments. TAM alone was effective on both R-27 and ineffective on Br-10, while UFT alone was ineffective on R-27 and Br-10. The combination antitumor activity was observed in R-27 but not in Br-10. When 5 mg of TAM per kg and 20 mg of UFT per kg as tegafur was administered daily po for 2 wk, there were no statistically significant differences between the concentration of 5-FU in UFT alone and UFT + TAM groups for the two strains. By the assay of ER and progesterone receptors using the same specimen, it was observed that ER was stable by the treatment of UFT, while ER was suppressed by the treatment of TAM in both tumor strains. In addition, this suppression of ER by TAM alone was enhanced by the combined treatment with UFT in both the strains.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
The calcium channel blocker nifedipine attenuates slow excitatory amino acid neurotoxicity.
High concentrations of potent N-methyl-D-aspartate (NMDA) agonists can trigger degeneration of cultured mouse cortical neurons after an exposure of only a few minutes; in contrast, selective non-NMDA agonists or low levels of NMDA agonists require exposures of several hours to induce comparable damage. The dihydropyridine calcium channel antagonist nifedipine was used to test whether this slow neurotoxicity is mediated by a calcium influx through voltage-gated channels. Nifedipine had little effect on the widespread neuronal degeneration induced by brief exposure to high concentrations of NMDA but substantially attenuated the neurotoxicity produced by 24-hour exposure to submaximal concentrations of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate, kainate, or quinolinate. Calcium ion influx through dihydropyridine-sensitive, voltage-dependent calcium channels may be an important step in the neuronal injury induced by the prolonged activation of NMDA or non-NMDA glutamate receptors.
Animals↗
Changes in the hormone receptors of human breast carcinoma xenografts in nude mice by treatment with cytotoxic agents.
We examined the effect of chemotherapeutic agents on the estrogen receptors (ER) of breast carcinomas in vivo using human breast carcinoma strains (Br-10, T-61) serially transplanted into nude mice. When the tumor size reached approximately 1 X 1 X 1 cm, mitomycin C (MMC) at doses of 1, 2 and 4.5 mg/kg and cyclophosphamide (CPA) at a dose of 120 mg/kg, were administered once intraperitoneally, and the ERs of the tumors were measured sequentially by the dextran-coated charcoal method. Four days after the MMC administration at above doses, the binding sites of ER in Br-10 were not reduced and binding affinity was not affected. When the changes in ER content with time after the treatment with 4.5 mg/kg MMC and 120 mg/kg CPA were investigated, the ER content was found to be stable until 4 days after the treatment with both drugs, although the growth of T-61 had been significantly inhibited by the drugs. From these findings, it seems reasonable to initiate chemotherapy before endocrine therapy, since the chemotherapeutic agents did not reduce the ER content of the breast cancer strains.
Animals↗
Continuous epidural infusion for postoperative mechanical ventilation.
We evaluated in analgesic and sedative effects of continuous epidural infusion of two analgesic regimens in ventilated patients following esophagectomy. Forty-six patients, divided into two treatment groups, received postoperative continuous epidural infusion of morphine, or that of a combination of bupivacaine and morphine. Assessments were made with the following indices: pain relief score, somnolence score, patient ventilator coordination score, and the number of supplemental administrations of analgesics and sedatives. No significant differences occurred in somnolence scores or patient ventilator coordination scores between the two groups, which revealed satisfactory sedation for mechanical ventilation. Patients receiving the combination of bupivacaine and morphine had significantly less pain postoperatively, requiring a smaller number of supplemental administrations of analgesics and sedatives ( P < 0.05). It is concluded that: 1) continuous epidural infusion of analgesics gives potent analgesia and sedation of ventilated patients following esophagectomy; 2) the combination of bupivacaine and morphine gives pain relief superior to morphine alone.
Journal Article↗
Antitumor activity and pharmacokinetics of a morpholino-anthracycline derivative (KRN8602) against human breast carcinoma xenografts serially transplanted into nude mice.
The antitumor activity and pharmacokinetics of (7R, 8S, 10S)-10-((3-deamino- 3-(4-morpholino)-2,3,6-trideoxy-alpha-L-lyxo-hexopyranosyl)oxy)-8- ethyl- 7,8,9,10-tetrahydro-1,6,7,8,11-pentahydroxy-5,12-naphthacenedione hydrochloride (KRN8602) were evaluated using five human breast carcinoma xenografts in nude mice. The maximum non-toxic dose of KRN8602 was 2 mg/kg by q4d x 3 intraperitoneal and peroral administration. KRN8602 showed significant antitumor activity against MX-1, which is less sensitive to adriamycin, with the chemotherapeutic indices of 13.0 for po administration and 9.5 for ip injection. Although KRN8602 also inhibited the growth of T-61 significantly, the antitumor activity of this agent against the other three breast carcinoma xenografts was limited. To elucidate this discrepancy, pharmacokinetic analysis and MTT assay were conducted using the KRN8602-sensitive MX-1 and KRN8602-insensitive R-27. While no differences were observed in the area under the curve and the peak concentration of KRN8602 for each tumor, a difference in the sensitivity of the tumor strains was obvious in MTT assay. The efficacy of this agent seemed to depend on the sensitivity of each type of tumor cell rather than the concentration of agent in tumor tissues. If it were possible to select patients with sensitive tumor cells to this agent by the MTT assay, the phase II trial might be completed within a short period by reducing the number of studied patients.
Animals↗
Cortical neurons containing somatostatin- or parvalbumin-like immunoreactivity are atypically vulnerable to excitotoxic injury in vitro.
We exposed murine cortical neuronal cell cultures for 24 hours to defined concentrations of N-methyl-D-aspartate (NMDA), kainate, or alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), and assessed the resultant neuronal degeneration quantitatively by the efflux of lactate dehydrogenase to the bathing medium. The small subpopulations of neurons that stained immunohistochemically for either somatostatin- or parvalbumin-like reactivity were atypically affected by these excitotoxins. Limited exposure to kainate or AMPA did little damage to the general neuronal population, but destroyed nearly all somatostatin- or parvalbumin-reactive cells. Conversely, these immunoreactive cells were more resistant to NMDA-induced injury than the general population. In view of reports suggesting that somatostatin- and parvalbumin-reactive cortical neurons may be preferentially damaged in Alzheimer's disease, these observations support a hypothesis that the overactivation of non-NMDA receptors could be involved in Alzheimer's disease pathogenesis.
Animals↗
Inherited deletion at Duchenne dystrophy locus in normal male.
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Chromosome Deletion↗
Prenatal diagnosis using deletion studies in Duchenne muscular dystrophy.
Accurate carrier testing and prenatal diagnosis in Duchenne muscular dystrophy (DMD) families is facilitated when an Xp21 deletion is found to be segregating within a family. We discuss the results of the DNA testing in two families, one in which DNA from affected males was available for study and the other in which no DNA from an affected male was available. Factors complicating the counselling of DMD deletion families are outlined.
Chromosome Deletion↗
Zinc neurotoxicity in cortical cell culture.
Large amounts of zinc are endogenously present in synaptic vesicles of mammalian central excitatory boutons, and are likely released during synaptic activity; transient elevations in extracellular zinc concentration exceeding several hundred micromolar may accompany intense neuronal excitation. Exposure of mature cortical cell cultures, in mice, to similar concentrations of zinc for several minutes resulted in widespread neuronal injury; the extent of injury was dependent on both the concentration of zinc, and the length of exposure. Quantitative neuronal cell counts suggested an approximate neurotoxic ED50 of 600 microM for a 15 min zinc exposure, and 225 microM for an 18-24 h exposure. High zinc concentrations or long exposure times resulted in the addition of glial injury to the neuronal injury; this glial injury could also be demonstrated in neuron-free glial cell cultures, and hence likely represented a direct effect of zinc rather than a consequence of neuronal injury. Neurons in immature cultures were relatively resistant to zinc-induced injury, suggesting that neuronal vulnerability to zinc increases with maturation in vitro. An early event associated with toxic exposure to zinc was gross neuronal swelling. This swelling was dependent on the presence of extracellular sodium, and, interestingly, could be delayed by the continued presence of zinc itself. Zinc-induced neuronal cell loss, however, occurred even when both sodium and calcium were absent during the exposure to zinc. The present results provide direct evidence that zinc might be a relatively potent, rapidly acting neurotoxin, and somewhat less potent gliotoxin, in the mammalian central nervous system. We suggest that zinc should be included on the growing list of endogenous toxins which may be involved in the acute pathogenesis of central neuronal, and possibly glial, cell loss in some disease states.
Animals↗
Mode of action of estra-1,3,5(10)-triene-3,17 beta-diol 3-benzoate 17-[4-(4-bis(2-chloroethyl)amino)phenyl)-1-oxobutoxy)acet ate) on human breast carcinoma xenografts in nude mice.
To elucidate the mode of action of busramustine (KM2210), 17 beta- and alpha-busramustine, estradiol and chlorambucil were used for experimental chemo- and endocrino-therapy against hormone-dependent (T-61) and independent (MX-1) human breast carcinomas serially transplanted into BALB/cA female nude mice. Busramustine was administered po daily for 3 weeks at doses of 12.5-300 mg/kg for the beta-isomer and 25-300 mg/kg for the alpha-isomer. Five to 50 mg of estradiol per kg was administered im once, and 3 to 6 mg of chlorambucil per kg was administered po daily for 3 weeks. All of the compounds were effective against estrogen receptor-positive T-61 with a clear dose-response relationship, while estrogen receptor-negative MX-1 was sensitive to all of the agents except estradiol. Since the alpha-isomer of busramustine was effective against both tumor lines, the mode of action of 17 beta-busramustine may not be related to estrogenic action by estradiol released from the maternal compound. However, 17 beta-busramustine generated the estrogen receptor system of T-61 tumor and resulted in the endometrial hyperplasia of tumor-bearing nude mice, suggesting that this compound also has estrogenic action on transplanted human breast carcinoma and tumor-bearing host mice, besides non-estrogenic antitumor activity on human breast carcinoma xenografts.
Animals↗