Oral contraceptives and risk of venous thromboembolism: impact of duration of use.
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Biomedical subjects
Publications and source records attributed to C L Chang.
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In this study, we determined the expression of protein kinase C (PKC) isoforms during trauma-induced decidualization. The findings revealed that at least five PKC isoforms (alpha, delta, zeta, iota and lambda) were present in both control and decidualized tissues. After trauma-stimulation, PKC alpha was down-modulated in the deciduomata but not in the myometrium. Down-modulation was compatible with the increase in cell mitosis which reached a maximum at 2-3 days. On the other hand, PKC zeta was not down-modulated. It was increased both in the deciduomata and myometrium, and paralleled the frequency of decidual cell mitosis. The PKC isoforms of delta, iota and lambda were also increased, but they were associated with the depression of cell mitosis. Therefore, these findings suggested that the variable expression of PKC isoforms in trauma-induced decidualizing tissue in pseudopregnant rats may be involved in the modulation of decidual cell growth.
Laryngospasm occurring after tracheal extubation in children is potentially dangerous. This study uses acupuncture with bloodletting at the Shao Shang (L 11) or Shang Yang (Li 1) acupoints to investigate whether this technique can prevent or treat laryngospasm. Seventy-six patients were randomly divided into two groups. Patients in the acupuncture group (n = 38) were treated with bilateral Shao Shang acupunctures at the end of the operation. Patients in the control group (n = 38) were not. The incidence of laryngospasm in the acupuncture group (5.3%) was less than that in the control group (23.7%) (p < 0.05). If laryngospasm developed, patients were immediately treated with acupuncture at either the Shao Shang or Shang Yang acupoints. As judged by an increase in peripheral oxygen saturation, the laryngospasm was relieved within 1 min of acupuncture in all patients. It is concluded that acupuncture with bloodletting at the Shao Shang acupoint may prevent and treat laryngospasm occurring after tracheal extubation in children.
STUDY OBJECTIVE: To assess age specific incidence and mortality of stroke, acute myocardial infarction (AMI), and idiopathic venous thromboembolism (VTE) associated with use of modern low dose combined oral contraceptives (OCs) and the interaction with smoking. DESIGN: Hospital-based case-control study. SETTING: Hospitals in Oxford region in the United Kingdom, which covered a defined population, during the period 1989-1993. METHODS: Relative risk estimates from the WHO Collaborative Study and observed incidence rates from the Oxford region were used to estimate age specific incidence of each disease among women without cardiovascular risk factors and model total cardiovascular incidence and mortality. RESULTS: Among women who did not use OCs, smoke nor had any other cardiovascular risk factors, total incidence of stroke and AMI were less than 2 events per 100,000 woman years in those aged 20-24 years and rose exponentially with age to 8 events per 100,000 among women aged 40-44 years. Incidence of idiopathic VTE among women who did not use OCs rose linearly with age (from 3.3 per 100,000 at ages 20-24 years to 5.8 per 100,000 at ages 40-44 years). The increased risk of idiopathic VTE associated with OC use among non-smokers constituted over 90% of all cardiovascular events for women aged 20-24 years and more than 60% in those aged 40-44 years. Fatal cardiovascular events were dominated by haemorrhagic stroke and AMI, and among OC users who smoked these two diseases accounted for 80% of cardiovascular deaths among women aged 20-24 years, rising to 97% among those aged 40-44 years. Cardiovascular mortality associated with smoking was greater than that associated with OC use at all ages. Attributable risk associated with OC use was 1 death per 370,000 users annually among women aged 20-24 years, 1 per 170,000 at ages 30-34 years, and 1 per 37,000 at ages 40-44 years. Among smokers, the cardiovascular mortality attributable to OC use was estimated to be about 1 per 100,000 users annually among women aged less than 35 years, and about 1 per 10,000 users annually among those above the age of 35 years. CONCLUSION: The incidence of fatal cardiovascular events among women aged less than 35 years is low. The VTE risk associated with OC use is the largest contributor to OC induced adverse effects. The potentially avoidable excess VTE risk associated with the newer progestogens desogestrel and gestodene would account for a substantial proportion of total cardiovascular morbidity in this age group. For women over age 35 years the absolute risks associated with OC use and smoking are greater because of the steeply rising incidence of arterial diseases. The combination of smoking and OC use among such women is associated with particularly increased risks. Any potential reduction in AMI or stroke risk with use of third generation OCs would be a more important consideration among older compared with younger women, particularly if they smoke. However, the mortality associated with smoking is far greater than that associated with OC use (of any type) at all ages.
Recently, we developed a new method to measure the resting level of superoxide anion in whole blood using an ultrasensitive chemiluminescence analyzer and lucigenin amplification. The advantage of this method is that the assay system can be performed in the absence of leukocyte isolation and stimulant administration. In this study, we applied this method to measure the blood resting levels of superoxide anion in 104 uremic patients on chronic hemodialysis (CHD) and 98 sex- and age-matched healthy controls to clarify the influence of HD on blood levels of superoxide anion. Simultaneously, the plasma levels of copper, zinc superoxide dismutase (Cu,Zn-SOD), glutathion peroxidase (GPX), myeloperoxidase (MPO) and lactoferrin (Lacto-F) were measured. The results showed that the basal blood levels of superoxide anion, Cu,Zn-SOD, and MPO in CHD patients were significantly greater than those of healthy controls. However, there was no difference in the basal plasma levels of Lacto-F and GPX between CHD patients and healthy controls. One session of HD further increased the blood levels of superoxide anion, MPO, Lacto-F and Cu,Zn-SOD but not GPX. These results suggest that the blood levels of superoxide anion are higher in CHD patients and further increase after one session of HD. This mechanism should be studied further.
BACKGROUND: Sudden and overwhelming increases in blood pressure (BP) and heart rate (HR) during incision of the scalp may give rise to morbidity or mortality in patients with intracranial pathology undergoing neurosurgery. A modification of the method proposed by Labat to abate this circumstantiality was applied in a group of patients receiving craniotomy. The modified method was to combine scalp circuit infiltration of local anesthetic with general anesthesia to control the hemodynamic response to craniotomy. METHODS: Twenty-six patients scheduled to undergo craniotomy were randomly divided into two groups. Patients whose conditions or their current medication that might affect the stability of hemodynamics were excluded. In group A patients (N = 16) 25-30 ml of 0.25% bupivacaine was used for scalp circuit infiltration on the operation side, while in those of group B (N = 10) the same volume of 0.9% normal saline was used. After induction, anesthesia was maintained with 0.6% to 1.2% end-tidal isoflurane (ET-Iso) and 50% N2O in oxygen (N2O:O2 = 2 l/min:2 l/min). The end-tidal CO2 was kept within the range of 25-30 mmHg. BP and HR were recorded every five min before incision and then every two min after incision until one hour after induction. ET-Iso was also recorded every two min throughout a period of sixty min. If the BP and HR increased above 20% of the baseline (10 min before incision), thiopental 2.5 mg/kg and fentanyl 2 micrograms/kg were administered. If hypertension became sustained, the isoflurane concentration was adjusted until an acceptable level was obtained. RESULTS: The mean BP during the surgery was 92 +/- 1 mmHg in group A and 92 +/- 7 mmHg in group B. The difference in BP between incision to 6 min after incision was statistically significant (P < 0.05). The mean HR during surgery was 101 +/- 5 beats/min in group B and 91 +/- 2 beats/min in group A, the difference of which was not statistically significant. All of the patients in group B required a deepened anesthesia to keep the BP and HR within the normal range, but no patient in group A had such need. The average concentration of ET-Iso during the 60 min period was 0.95 +/- 0.12% in group B and 0.41 +/- 0.01% in group A, respectively. The difference was statistically significant (P < 0.05). CONCLUSIONS: Our results showed that scalp circuit infiltration with 0.25% bupivacaine significantly improved the cardiovascular stability and reduced the requirement of isoflurane during craniotomy. The routine use of bupivacaine scalp circuit infiltration in patients undergoing craniotomy should be considered.
Genitourinary tuberculosis (TB) rarely involves the adrenal gland. A 67-year-old man presented with progressively hyperpigmented skin and an enlarged mass over both testes. Early morning plasma cortisol concentration was low and adrenocorticotropic hormone (ACTH) concentration was high. A rapid ACTH stimulation test revealed the absence of plasma cortisol response and confirmed a diagnosis of primary adrenocortical insufficiency. An abdomen computed tomography (CT) scan disclosed enlargement of the right adrenal gland and punctuate calcification over the left one. This is compatible with tuberculous adrenalitis. Currettage biopsy of the prostate demonstrated chronic granulomatous inflammation with Langerhan's giant cells, but without TB bacilli. Anti-TB treatment, in addition to glucocorticoid and mineralocorticoid replacement, was administered. The testicular mass decreased progressively though the results of a subsequent ACTH stimulation test, six months later, disclosed no significant change. A follow-up CT scan, one and a half years later, showed a decrease in the size of the right adrenal mass.
To manage fetal tachyarrhythmia induced hydrops, both a correct diagnosis and adequate intrauterine therapy are fundamentally important. We present a 32-week-gestational-age hydropic fetus with supraventricular tachycardia who responded dramatically after transplacental administration of high dose digoxin (1 mg intravenously daily). The baby was born at 36 weeks' gestation followed by a successful postnatal conversion. Prenatal fetal echocardiography is emphasized in determining appropriate treatment and monitoring fetal well-being which in this case resulted in a good outcome.
The effect of a novel pentacyclic triterpene, 1-decarboxy-3-oxo-ceanothic acid (DOCA) on DNA synthesis, DNA degradation and programmed cell death was examined in human ovarian adenocarcinoma (OVCAR-3) cells. OVCAR-3 cells exposed to various concentrations of DOCA for 30 h displayed a dose-dependent inhibition of DNA synthesis. Morphologically, treatment with 10 microg/ml of DOCA for 24 h and 72 h resulted respectively in reduction in cell volume and condensation of nuclear structures. By agarose gel analysis, DNA fragmentation with the characteristic pattern of inter-nucleosomal ladder was observed after cells were treated with 2.5 microg/ml of DOCA for 24 h. Both cell death and DNA fragmentation caused by this compound were partially inhibited by the protein synthesis inhibitor cycloheximide, suggesting that the apoptotic process caused by DOCA requires synthesis of new proteins. On the other hand, no apparent double-stranded DNA breaks were detected after cells were incubated with 2.5 microg/ml of DOCA for 24 h, indicating that DNA damage was not a preceding event for apoptosis induced by this compound. Taken together, our results demonstrate that the cytotoxic effect of DOCA is mediated, at least in part, by the induction of apoptosis.
BACKGROUND: Nitric Oxide (NO), an endogenous messenger produced by the enzyme nitric oxide synthase (NOS), is recently introduced to be involved in inhalational anesthesia. We have previously reported that a specific NOS inhibitor, nitroG-L-arginine methyl ester (L-NAME), reduces the value of minimum alveolar concentration (MAC) for isoflurane anesthesia in rabbits. The purpose of this study is to evaluate the effects of the NOS inhibitor, L-NAME, on isoflurane MAC and NOS activity in rats. METHODS: Adult Wistar rats receiving isoflurane inhalation were randomly divided into two groups, with eight rats in each group. In the study group, L-NAME 30 mg/kg was given 60 min before the inhalation of isoflurane. Normal saline was given to the control group instead. The data of MAC, blood pressure (BP), and heart rate (HR) were recorded. The vital signs, such as EtCO2, PaO2, and temperature, were maintained within normal ranges. The activity of NOS in cerebellum was assessed by measuring the conversion of L-[3H] arginine to L-[3H] citrulline. All data were presented as mean +/- SD. Statistical analysis was performed using Student's t-test, where P < 0.05 was considered significant. RESULTS: In the presence of L-NAME (30 mg/kg), the MAC for isoflurane was markedly reduced from 1.6 +/- 0.20% (study group) to 1.0 +/- 0.09% (control group) (P < 0.05). The activity of cNOS in cerebellum was 220.09 +/- 23.64 (pmol/mg protein/30 min) in the control group, and in contrast a sharp reduction as low as to 115.40 +/- 24.85 (pmol/mg protein/30 min) was seen in the study group. CONCLUSIONS: The involvement of NO in the mechanism of isoflurane anesthesia can be demonstrated by the fact that the NOS inhibitor, L-NAME reduces the level of MAC and the cerebral NOS activity in rats.
Our previous data showed that at least five PKC isoforms (alpha, delta, zeta, lambda and tau) were present in the decidualization. In this study, we then localized the PKC alpha and zeta by immunohistochemistry in the decidualized uterine tissues. The decidualized uterine tissues were induced by trauma-stimulation and fixed in formalin. The immunofluorescence were photographed by confocal microscope. The data revealed that the fluorescence of PKC alpha was present in the deciduomata and myometrium. In the deciduomata, PKC alpha was mainly located in the surrounding nuclear. This phenomenon of localization was especially performed on day 2 and 3 of the decidualization, just on the time of higher frequence of cell mitosis. Since the myometrium with hypertrophy did not display the phenomenon of perinuclear localization, these suggested that the expression and localization of PKC alpha may be associated with the cell proliferation. On the other hand, the PKC zeta was also present and distributed broadly in the deciduomata and myometrium. This expression was increased and similar to the previous Western blot studies. Thus, the data confirmed that the various expression and localization of PKC isoforms may be correlated with the development of deciduomata.
The specific activities of protein kinase C (PKC) and protein tyrosine kinase (PTK) were determined in the decidualized uterine tissue of pseudopregnant rat on day 5 of decidualization. We found that the activity of the cytosolic PKC was significantly lower in decidualized uterine tissue as compared with that of the controlateral untreated uterine tissues (1.5 +/- 1.4 versus 57.5 +/- 4.1 pmol 32P/min/mg, P < 0.001), while the PKC activity in particulate fraction was not significantly different (124.8 +/- 14.5 versus 236.8 +/- 88.6 pmol 32P/min/mg) concerning protein concentration. The reduced expression of the cytosolic PKC activity was observed on all five individual rats. In contrast, the decidualized uterine tissue showed similar cytosolic PTK activity as compared with the controlateral untreated uterine tissues (20.1 +/- 3.0 versus 20.6 +/- 3.2 pmol 32P/min/mg protein), and similar in particulate PTK activity (42.5 +/- 9.0 versus 36.8 +/- 5.1 pmol 32P/min/g protein). These results indicate that cytosolic PKC activity may be involved in modulation of decidual growth.
In this study, Jen-Chung (J-C) point was stimulated by electroacupuncture (EA) in 10 patients, and by placebo treatment in 10 controls, immediately after termination of inhalation for 15 min. During the postoperative recovery period, plasma catecholamine (CA) levels were assessed before (0) and 15 and 30 min after treatment. The time from cessation of inhalation to the first eye opening and to extubation did not differ between groups. The plasma catecholamine levels increased by 30% from 0 to 15 min in the control group but decreased by 6% in the EA group. The levels at 30 min were approximately the same as at time 0. The change in catecholamine levels from 0 to 15 min was significantly lower (P < 0.02) in the EA groups than the control group.
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Video-assisted thoracoscopic surgery (VATS) has been performed during ganglionectomy and bullectomy and usually requires a collapsed or immobilized lung. Transtracheal insufflation of oxygen (TRIO) maintains an immobilized lung, adequate oxygenation, and partial CO2 elimination but has never been used for VATS. We have simplified the TRIO design with a catheter inserted through the lumen of the orotracheal tube in what we call "transorotracheal tube TRIO" (TRIO-TOTT) and investigated its clinical use on simple VATS. Eleven patients undergoing bullectomy for primary simple pneumothorax (PSP) were studied. During the performance of VATS, a 12-gauge suction catheter was inserted as our modification and connected to the gas outlet of an anesthetic machine. The flow rate of oxygen was maintained at 10 L/min. Blood gas was collected prior to TRIO-TOTT, during TRIO-TOTT at 5, 10, 15, and 20 min, and 5 min after TRIO-TOTT. The blood gas data showed excellent oxygenation while the PaCO2 increased at a rate of 1.2 mm Hg/min compared to 3-4 mm Hg/min for apnea oxygenation. After 20 min, the mean +/- SEM PaO2 and PaCO2 were 428 +/- 27 and 65.0 +/- 2.6 mm Hg, respectively. We conclude that TRIO-TOTT is a simple, safe, and effective ventilation method for simple VATS.
An investigation was undertaken to study the relationship between change in gastric lesion induced by cold-restraint stress and brain dopamine (DA) activity in male rat with chronic hyperprolactinemia. Male rats of Wistar strain were divided into two groups: one received extra two pieces of anterior pituitary (AP) from its littermates, the other grafted with several pieces of muscle served as control. Experiment I: From the 5th day to 40th day after transplantation, the levels of serum prolactin (PRL) in the AP-grafted group were higher than those of control (p < 0.05 or p < 0.01). Experiment II: On the 40th day after transplantation, AP-grafted and control rats were restrained and placed supine in a ventilated refrigerator with an ambient temperature of 5 degrees C for 3 hrs. Although gastric mucosal ulceration was observed in both groups, the ulcer index (including total number and length of gastric mucosal ulceration) was lower in AP-grafted group than that in control group (p < 0.05 or p < 0.01). Experiment III: On the 40th day after transplantation, all rats were divided into AP-grafted and muscle-grafted rats. Subsequently, they were allowed to expose to cold-plus-restraint stress and unstress (room temperature: 24 +/- 1 degrees C) respectively. After stress and unstress, all animals were immediately sacrificed by decapitation, the brains were dissected with Palkovits' micropunch technique. DA and its metabolites, DOPAC content in Nucleus accumbens (NAc) area of brain were assayed by HPLC with electrochemical detection. These results showed that concentrations of DA, DOPAC and their ratios (DOPAC/DA) in the NAc area of brain, were not statistically different under room temperature condition between muscle-grafted and AP-grafted rats. The DOPAC/DA ratio in both groups showed significant increase in the brain's NAc area under cold-restraint stress condition as compared with unstress condition. But AP-grafted rats exhibited significantly higher DOPAC content in the brain's NAc area when compared with muscle-grafted rats under cold-restraint stress condition (171.7 +/- 22.1 versus 101.5 +/- 14.2 ng/mg protein, p < 0.05). According to these findings, we suggest that reduced effect of chronic high serum PRL level from extra pituitary grafts on gastric mucosal ulceration produced by cold-restraint stress is probably mediated via Nucleus accumbens dopaminergic neuronal mechanism.
BACKGROUND: Controlled-release morphine (MST) given twice daily provides a simpler and more convenient treatment regimen than 4-hourly opioid administration for the control of cancer pain. Recently, a new formulation of transdermal fentanyl (TDF) has been developed which provides a new route for the treatment of cancer pain. The present study was designed to compare the analgesic efficacy, safety and adverse effects of MST and TDF in the management of chronic cancer pain. METHODS: In this open, comparative and randomized study, patients were treated with oral morphine hydrochloride immediate-release (MHIR) in the stabilization phase and then the prescription was switched to MST or TDF for 14 days in the treatment phase. Oral MHIR was provided as rescue medication for breakthrough pain. Assessments of the pain intensity, pain frequency, degree of pain improvement, profile of mood states, quality of sleep, activity status and adverse effects were performed before and after the stabilization phase and before and after the treatment phase. RESULTS: Forty of 47 cancer patients completed the study with 20 patients in each group. There were significant (p < 0.05) improvements in pain intensity, pain frequency, mood states and quality of sleep in both groups before and after treatment, while improvement in the activity status was not significant. No specific adverse effects were encountered except for drowsiness which occurred in 6 patients treated with MST and 5 treated with TDF (p < 0.05). Insomnia was significantly improved (p < 0.05) with both regimens compared with that in the period before treatment. There were no significant differences between the two study groups in analgesic efficacy or adverse effects. CONCLUSIONS: These results suggest that TDF and MSt are safe and effective analgesics for the management of chronic cancer pain. However, TDF provides a simpler and more convenient treatment for those patients with severe nausea, vomiting or dysphagia.
BACKGROUND: Recently, some studies suggested that nitric oxide (NO) plays a role as a mediator in the central nociceptive pathways and is possibly involved the mechanisms of anesthesia and wakefulness. Inhibition of the L-arginine-NO pathway in the central nervous system may result in an anesthetic, analgesic, or sedative effect. The aim of the present study was to evaluate the effects of the nitric oxide synthase inhibitor (NOSI), nitroG-L-arginine methyl ester (L-NAME), on the threshold for isoflurane anesthesia in rabbits. METHODS: Sixteen New Zealand rabbits were randomly divided into two groups, with eight rabbits in each group. In the study group, a dose of L-NAME 30 mg/kg was injected i.v. daily as pretreatment on three consecutive days, and the fourth dose of L-NAME was given 30 min before the study began. Normal saline was given to the control group. Data of minimal alveolar concentration (MAC), blood pressure (BP), and heart rate (HR) were collected from both groups. Vital signs, such as EtCO2, O2 saturation, and temperature, were maintained within the normal range. All data were described as mean +/- SEM. Statistical analysis was performed using Student's t-test, where p < 0.05 was considered significant. RESULTS: MAC of isoflurane in the control group was 1.90 +/- 0.12%. MAC of the L-NAME group was 1.70 +/- 0.22%, significantly lower than the control group (p < 0.05). CONCLUSIONS: Our preliminary result shows that the MAC of isoflurane in animals treated with L-NAME was lower than that in the control group. It is suggested that inhibition of the nitric oxide pathway may enhance the effect of isoflurane.