The basic mechanisms by which ephedrine is preferred over other vasopressors in obstetric anesthesia have not been clearly defined. We examined the sympathomimetic effects of l-ephedrine, currently ...used as a vasopressor, and d-pseudoephedrine, currently used as a decongestant. In anesthetized rats, l-ephedrine and d-pseudoephedrine caused dose-dependent increases in arterial blood pressure and heart rate, and these effects disappeared after destruction of the sympathetic nerve terminals with 6-hydroxydopamine (6-OHDA) pretreatment. The two ephedrine isomers produced concentration-dependent increases in tension of anococcygeal muscle and sinus rate of right atrium from rats. However, the anococcygeal and atrial responses to d-pseudoephedrine were abolished after 6-OHDA pretreatment, whereas approximately 50% of the responses to l-ephedrine were 6-OHDA-resistant. In human umbilical artery and vein, the two isomers failed to generate any contraction when given at the concentration that is capable of producing significant effects on anococcygeal and atrial tissues. Although direct adrenoceptor activation with l-ephedrine was detectable at tissue levels, the pressor response in vivo was entirely attributable to norepinephrine release from sympathetic nerves. This indirect mechanism could partly explain why l-ephedrine is better at increasing maternal arterial blood pressure while preserving the uteroplacental blood flow that is devoid of the involvement of the sympathetic innervation.
Although GC therapy (the traditional 4-week4Wregimen)is administered to urothelial cancer patients, discontinuation of gemcitabine after 15 days of administration is a problem. One solution is to use ...a 3-week (3W) regimen. Because a Japanese study comparing the 3W to the 4W regimens reported the lower efficacy and safety of the 3W regimen, we compared these regimens in a retrospective study. Leukopenia of Grade≥occurred in 18% and 18% of cases and anemia of Grade≥3 occurred in 28% and 39% of cases treated with the 3W and 4W regimens, respectively. On the other hand, thrombocytopenia of Grade≥3 occurred in 13% and 39% of cases treated with the 3W and 4W regimens, respectively (p< 0.001). In addition, overall survival was 14.8 months and 15.0 months for the 3W and 4W regimens, respectively (p=0.97). Thus, the 3W regimen as an alternative treatment instead of the 4W regimen is considered a highly tolerated regimen.
The purpose of this study was to extract the risk factors for GradeB3 leukopenia induced by docetaxel plus prednisolone (DP)therapy administered to patients with castration-resistant prostate cancer. ...Rates of 59% for GradeB3 leukopenia and 11% for FN were observed. On multivariate analysis, the pretreatment white blood cell count(OR=0.502, 95%CI: 0.292- 0.862, p=0.01)was significantly associated with severe leukopenia induced by DP therapy. In addition, on univariate analysis, the pretreatment platelet count, disease extent, and bilirubin level were significant factors. We consider it necessary to immediately treat patients with these risks with G-CSF.
Bradycardia is one of the inevitable and undesirable responses when the muscle weakness induced by nondepolarizing muscle relaxants is reversed by AChE inhibitors. The current study was designed to ...compare the bradycardiac effects of the two AChE inhibitors used widely in clinical anesthesia, neostigmine and edrophonium. Isolated, spontaneously beating guinea pig right atrial preparations were used as the experimental model, and in some cases, electrical field stimulation was utilized to stimulate parasympathetic nerve terminals within the atria. Neostigmine decreased the spontaneously beating rate in a concentration-dependent manner at concentrations up to 10 microM. At higher concentrations, the agent restored the beating rate to the predrug control level. Atropine abolished the biphasic response of the atrium to neostigmine. In contrast, edrophonium had no effect on the spontaneous beating rate. However, edrophonium (3 microM) potentiated the field stimulation-induced negative chronotropic effect. Tetrodotoxin did not inhibit the chronotropic effect of neostigmine. Both neostigmine and edrophonium at higher concentrations inhibited the negative chronotropic effect of carbachol. In conclusion, neostigmine possesses potential dual effects on cardiac muscarinic ACh receptors. Low concentrations of neostigmine may stimulate the receptors directly, and at higher concentrations neostigmine may act as an antimuscarinic agent. On the other hand, edrophonium may inhibit the cardiac muscarinic ACh receptors exclusively without stimulating the receptors. These results could at least partially explain the difference between the bradycardiac effects of the agents observed clinically.
The effect of prostaglandin E
1
(PGE
1
) on the spontaneous phasic contraction of the rat isolated portal vein was studied.
The isolated portal vein exhibited spontaneous phasic contractions. Removal ...of Ca
2+
from Krebs‐Ringer solution or application of nifedipine abolished the spontaneous contraction, indicating that the contraction depends exclusively on Ca
2+
influx through L‐type Ca
2+
channels. On the other hand, cyclopiazonic acid (CPA), a specific inhibitor of Ca
2+
‐ATPase of sarcoplasmic reticulum (SR) increased the amplitude of the contractions, suggesting that the SR regulates the spontaneous contractions negatively by sequestration of Ca
2+
entering through L‐type Ca
2+
channels and buffering the rise in cytosolic Ca
2+
.
PGE
1
increased the amplitude of the spontaneous contraction in a concentration‐dependent manner without affecting the resting tension. The effect was completely abolished by nifedipine. Bay K 8644 and phenylephrine (PE) also increased the amplitude of the contraction in a concentration‐dependent manner. PGE
1
at a concentration of 1 μ
m
, Bay K 8644 at 100 n
m
and PE at 30 n
m
doubled the amplitude, respectively.
Pretreatment with 1 μ
m
CPA abolished the effect of PGE
1
, but the effects of Bay K 8644 and PE were not inhibited by pretreatment with CPA. In contrast, 10 μ
m
ryanodine attenuated the effect of PE without affecting the contractile effect of PGE
1
.
When the SR was depleted of Ca
2+
by repeated applications of caffeine in a nominally Ca
2+
‐free Krebs‐Ringer solution, it took about 120 s to restore the spontaneous contraction after addition of Ca
2+
into the solution. In CPA‐treated veins, the time taken to restore the contraction was shortened significantly. Pretreatment with 1 μ
m
PGE
1
shortened the time to the same extent as pretreatment with CPA did.
These results suggest that PGE
1
increases the amplitude of the spontaneous phasic contraction by a different mechanism from those by which PE and Bay K 8644 increase it. Inhibition of Ca
2+
‐ATPase of the SR might be involved in the vasoactive effect of PGE
1
.
British Journal of Pharmacology
(1997)
120
, 1419–1426; doi:
10.1038/sj.bjp.0701051
The effect of prostaglandin E1 (PGE1) on the spontaneous phasic contraction of the rat isolated portal vein was studied.
The isolated portal vein exhibited spontaneous phasic contractions. Removal of ...Ca2+ from Krebs‐Ringer solution or application of nifedipine abolished the spontaneous contraction, indicating that the contraction depends exclusively on Ca2+ influx through L‐type Ca2+ channels. On the other hand, cyclopiazonic acid (CPA), a specific inhibitor of Ca2+‐ATPase of sarcoplasmic reticulum (SR) increased the amplitude of the contractions, suggesting that the SR regulates the spontaneous contractions negatively by sequestration of Ca2+ entering through L‐type Ca2+ channels and buffering the rise in cytosolic Ca2+.
PGE1 increased the amplitude of the spontaneous contraction in a concentration‐dependent manner without affecting the resting tension. The effect was completely abolished by nifedipine. Bay K 8644 and phenylephrine (PE) also increased the amplitude of the contraction in a concentration‐dependent manner. PGE1 at a concentration of 1 μm, Bay K 8644 at 100 nm and PE at 30 nm doubled the amplitude, respectively.
Pretreatment with 1 μm CPA abolished the effect of PGE1, but the effects of Bay K 8644 and PE were not inhibited by pretreatment with CPA. In contrast, 10 μm ryanodine attenuated the effect of PE without affecting the contractile effect of PGE1.
When the SR was depleted of Ca2+ by repeated applications of caffeine in a nominally Ca2+‐free Krebs‐Ringer solution, it took about 120 s to restore the spontaneous contraction after addition of Ca2+ into the solution. In CPA‐treated veins, the time taken to restore the contraction was shortened significantly. Pretreatment with 1 μm PGE1 shortened the time to the same extent as pretreatment with CPA did.
These results suggest that PGE1 increases the amplitude of the spontaneous phasic contraction by a different mechanism from those by which PE and Bay K 8644 increase it. Inhibition of Ca2+‐ATPase of the SR might be involved in the vasoactive effect of PGE1.
British Journal of Pharmacology (1997) 120, 1419–1426; doi:10.1038/sj.bjp.0701051
To evaluate the technical feasibility of the transfemoral approach using a 3.5-Fr catheter system for transcatheter arterial chemoembolization (TACE) in patients with hepatocellular carcinoma (HCC).
...This study included 81 patients with unresectable HCC who underwent transfemoral TACE using a 3.5-Fr catheter system without a sheath between August 2008 and June 2010. A 2.0-Fr microcatheter was used within a 3.5-Fr catheter in all cases. After completion of TACE, manual compression was applied to the puncture site for 5min, and patients were kept supine for 1h. The success rate and periprocedural complications of TACE were evaluated.
Transfemoral TACE with a 3.5-Fr catheter system was carried out in 103 transfemoral TACE sessions. TACE was performed for 103 subsegmental arteries, 19 segmental arteries, 13 lobar arteries, 8 right inferior phrenic arteries, 1 left inferior phrenic artery, and 1 inferior pancreatico-duodenal artery. Image quality in all hepatic angiograms using 3.5-Fr catheters was satisfactory. Technical success was achieved in 97 (94%) out of 103 procedures. In only 1 patient, it took 10min to achieve hemostasis. There were no periprocedural complications.
Transfemoral TACE using a 3.5-Fr catheter system is technically feasible and enables early ambulation safely in patients with HCC.
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