Midline versus paramedian mandibulotomy for tongue cancer surgery: analysis of complications.

Midline and paramedian mandibulotomies both have distinct anatomical and surgical strengths. A retrospective study was performed at Chang Gung Memorial Hospital, Linkou Branch between 2014 and 2019 to investigate how the osteotomy site (midline (n = 221) or paramedian (n = 44)) and type (straight, notched, or stair-stepped) affect postoperative and post-radiotherapy complications in patients undergoing wide excision of tongue cancer with flap reconstruction. Midline mandibulotomies were predominantly of the straight osteotomy type, while paramedian mandibulotomies were mostly notched type (P < 0.001). Comparably low elective tooth extraction rates were found in both approaches (P = 0.556). Paramedian mandibulotomy showed a higher osteoradionecrosis rate (P = 0.026), but there was no significance in the sub-analysis of individual types. Paramedian sites were associated with more early infection (P = 0.036) and plate exposure (P = 0.036) than midline sites with the straight osteotomy type, but complication rates did not differ significantly for the notched and stair-stepped types. Paramedian sites (P = 0.020) and notched types (P = 0.006) were associated with higher odds of osteoradionecrosis in the univariable logistic regression analysis, but only the notched type remained significant in the multivariable analysis (P = 0.048). In conclusion, paramedian sites increased the rate of osteoradionecrosis, and correlation with the osteotomy type resulted in more osteoradionecrosis in notched types and more complications in straight paramedian mandibulotomies.

Antibiotic resistance and molecular typing of Photobacterium damselae subsp. damselae, isolated from seafood.

AIM: The objectives of our study is to determinate the antibiotic susceptibility of this organism to different antibiotics to determine the discriminatory power of the molecular typing methods. METHODS AND RESULTS: In this study, 50 Photobacterium damselae subsp. damselae isolates from Scomber australasicus and Rachycentron canadum were collected in Taiwan and their resistance to 15 different antimicrobial agents was determined. In addition, random amplification of polymorphic DNA (RAPD) and pulsed-field gel electrolysis (PFGE) were performed to study the epidemiology and clonal relationship of P. damselae subsp. damselae. The results showed that the 50 isolates generated 25 typeable profiles with multidrug resistance to 3-7 antimicrobials. The results also indicate that the RAPD and PFGE methods have high discriminatory power for molecular subtyping. CONCLUSION: Photobacterium damselae subsp. damselae isolates from fish to examine for multidrug resistance to antimicrobials. RAPD and PFGE methods revealed the high discriminatory power for molecular subtyping and provided information that could be used for risk assessment of P. damselae subsp. damselae infections. SIGNIFICANCE AND IMPACT OF THE STUDY: These results may help in epidemiological investigations of P. damselae subsp. damselae and may be useful in controlling or treating P. damselae subsp. damselae infections in aquaculture and clinical therapy.

Normal-sized ovarian papillary serous carcinoma: a case report.

A normal-sized ovarian papillary serous carcinoma is rare. We present the case of a 46-year-old woman with progressive abdominal fullness of one week's duration. The medical evaluation revealed abdominal carcinomatosis with normal-sized ovaries and an elevated serum CA-125 level of 147,365.8 U/ml. Cytoreductive surgery (hysterectomy, bilateral salpingo-oophorectomy, omentectomy, lymphadenectomy, infracolic omentectomy, peritoneal biopsy, washing cytology, and appendectomy) was performed. The histologic examination revealed an ovarian serous papillary carcinoma. Adjuvant chemotherapy was administered. The serum CA-125 level decreased after completion of treatment. Normal-sized ovarian serous surface papillary carcinomas should be kept in mind as an origin of disease in patients who have peritoneal carcinomatosis, which sometimes is a diagnostic dilemma of the disease source. We report this case to emphasize the clinical symptoms and importance of the early and accurate diagnosis of a normal-sized ovarian papillary serous carcinoma.

A novel defense mechanism that is activated on amyloid-beta insult to mediate cell survival: role of SGK1-STAT1/STAT2 signaling.

Amyloid-beta (Abeta) is known to induce apoptotic cell death and its underlying mechanism has been studied extensively, but the endogenous protection mechanism that results from Abeta insult is less known. In this study, we have found that Abeta(1-42) produced a dose-dependent decrease in cell viability and dose-dependent increase in apoptotic cell death in PC12 cells. Meanwhile, Abeta(1-42) (0.1 muM) increased the phosphorylation of serum- and glucocorticoid-inducible kinase1 (SGK1) at Ser-78 specifically. A parallel increase in ERK1/2, STAT1 and STAT2 phosphorylation and the anti-apoptotic gene Mcl-1 expression was also observed. Transfection of rat siRNAs against ERK1/2, SGK1, STAT1 and STAT2 abolished these effects of Abeta. Transfection of sgkS78D, the constitutively active SGK1, dose-dependently protected against Abeta-induced apoptosis and dose-dependently increased the expression of Mcl-1. SGK1 activation further phosphorylates STAT1 at Tyr-701 and Ser-727 directly, and activates STAT2 at Tyr-690 indirectly. Phosphorylation of STAT1/STAT2 upregulated Mcl-1 expression which in turn protected against Abeta-induced apoptosis. But Mcl-1 siRNA transfection enhanced Abeta-induced apoptosis. Mutation of SGK1 at Ser-78 blocked the effect of Abeta on STAT1/STAT2 phosphorylation and Mcl-1 expression. Further, mutation of STAT1/STAT2 prevented the effect of both Abeta and SGK1 on Mcl-1 expression. These results together showed a novel endogenous protection mechanism that is activated on Abeta insult to mediate cell survival.

Efficacy of electrolysed oxidizing water in inactivating Vibrio parahaemolyticus on kitchen cutting boards and food contact surfaces.

AIM: To determine the efficacy of electrolysed oxidizing (EO) water in inactivating Vibrio parahaemolyticus on kitchen cutting boards and food contact surfaces. METHODS AND RESULTS: Cutting boards (bamboo, wood and plastic) and food contact surfaces (stainless steel and glazed ceramic tile) were inoculated with V. parahaemolyticus. Viable cells of V. parahaemolyticus were detected on all cutting boards and food contact surfaces after 10 and 30 min, respectively, at room temperatures. Soaking inoculated food contact surfaces and cutting boards in distilled water for 1 and 3 min, respectively, resulted in various reductions of V. parahaemolyticus, but failed to remove the organism completely from surfaces. However, the treatment of EO water [pH 2.7, chlorine 40 ppm, oxidation-reduction potential 1151 mV] for 30, 45, and 60 s, completely inactivated V. parahaemolyticus on stainless steel, ceramic tile, and plastic cutting boards, respectively. CONCLUSIONS: EO water could be used as a disinfecting agent for inactivating V. parahaemolyticus on plastic and wood cutting boards and food contact surfaces. SIGNIFICANCE AND IMPACT OF THE STUDY: Rinsing the food contact surfaces with EO water or soaking cutting boards in EO water for up to 5 min could be a simple strategy to reduce cross-contamination of V. parahaemolyticus during food preparation.

Pulsed-field gel electrophoresis, plasmid profiles and phage types for the human isolates of Salmonella enterica serovar Enteritidis obtained over 13 years in Taiwan.

AIMS: Plasmid profile, phage typing, and pulsed-field gel electrophoresis (PFGE) patterns of 124 Salmonella Enteritidis strains isolated in 1998-2002 in Taiwan were analysed and the results were compared with those of the 63 strains obtained in 1991-1997, so that molecular subtypes and epidemic strains for Salmonella Enteritidis over a 13-year period (1991-2002) could be elucidated. METHODS AND RESULTS: A total of 124 strains of Salmonella Enteritidis isolated from human in Taiwan between 1998 and 2002 were analysed by PFGE, plasmid analysis and phage typing. The results obtained were compared with those of the 63 strains obtained in 1991-1997, so that the clonal relationships for a total of 187 strains obtained over 13 years could be elucidated. For PFGE, restriction enzymes XbaI, SpeI and NotI were used for chromosomal DNA digestion. Results showed 28 PFGE pattern combinations for the 187 Salmonella strains. Of them, pattern X3S3N3 was the major subtype as 130 strains isolated from different locations during 1991-2002 showed this PFGE pattern. For all these 187 strains, the genetic similarity was higher than 80%. Plasmid analysis showed 17 distinct types, which consist of one to four plasmids and the predominant phage type of those strains was PT4 (71.6%) and PT6a (13.4%). The three methods identified different degrees of polymorphism in the following order: plasmid profile (18 types, D = 0.659) > PFGE (28 types, D = 0.512) > phage typing (13 types, D = 0.438). As PFGE patterns, phage type and plasmid profile were combined for subtyping, the 187 strains could be grouped into 46 subtypes and the discriminatory index was raised to 0.795. For these 46 subtypes, the predominant one was X3S3N3/P1/PT4, which contained 77 (41%) isolates. CONCLUSIONS: Most of the Salmonella Enteritidis strains from sporadic cases were with pattern X3S3N3. They were the prevalent and may be the epidemic strains found in Taiwan during 1991-2002. The present study suggested that the several variants were derived from a single clonal line and the genome for strains of Salmonella Enteritidis are highly conserved over a 13-year period (1991-2002). SIGNIFICANCE AND IMPACT OF THE STUDY: The results obtained here are useful for epidemiolgical study of salmonellosis caused by Salmonella Enteritidis in Taiwan. Comparing the data of the present study with those obtained for strains from other countries, the major subtypes for Salmonella Enteritidis infection in the world can be elucidated.

Hypoxic preconditioning attenuated in kainic acid-induced neurotoxicity in rat hippocampus.

The neuroprotective effect of hypoxic preconditioning on kainate (KA)-induced neurotoxicity, including apoptosis and necrosis, was investigated in rat hippocampus. Female Wistar-Kyoto rats were subjected to 380 mm Hg in an altitude chamber for 15 h/day for 28 days. Intrahippocampal infusion of KA was performed in chloral hydrate anesthetized rats, which acutely elevated 2,3-dihydroxybenzoic acid levels in normoxic rats. Seven days after the infusion, KA increased lipid peroxidation in the infused hippocampus and resulted in hippocampal CA3 neuronal loss. A 4-week hypoxic preconditioning attenuated KA-induced elevation in hydroxyl radical formation and lipid peroxidation as well as KA-induced neuronal loss. The effects of hypoxic preconditioning on KA-induced apoptosis and necrosis were investigated further. Two hours after KA infusion, cytosolic cytochrome c content was increased in the infused hippocampus. Twenty-four hours after KA infusion, pyknotic nuclei, cellular shrinkage, and cytoplasmic disintegration, but not TUNEL-positive staining, were observed in the CA3 region of hippocampus. Forty-eight hours after KA infusion, both DNA smear and DNA fragmentation were demonstrated in the infused hippocampus. Furthermore, TUNEL-positive cells, indicative of apoptosis, in the infused hippocampus were detected 72 h after KA infusion. Hypoxic pretreatment significantly reduced necrotic-like events in the KA-infused hippocampus. Moreover, hypoxic preconditioning attenuated apoptosis induced by KA infusion, including elevation in cytosolic cytochrome c content, TUNEL-positive cells, and DNA fragmentation. Our data suggest that hypoxic preconditioning may exert its neuroprotection of KA-induced oxidative injuries via attenuating both apoptosis and necrosis in rat hippocampus.

Hydrogen peroxide increases the activity of rat sympathetic preganglionic neurons in vivo and in vitro.

Reactive oxygen species (ROS) have been shown to modulate neuronal synaptic transmission and have also been implicated in cardiovascular diseases such as hypertension. The hypothesis that H(2)O(2) acting on sympathetic preganglionic neurons (SPNs) affects spinal sympathetic outflow was tested in the present study. H(2)O(2) was applied intrathecally via an implanted cannula to the T7-T9 segments of urethane-anesthetized rats. Blood pressure and heart rate were used as indices to evaluate the spinal sympathetic effects of H(2)O(2) in vivo. Intrathecal H(2)O(2) (100-1000 nmol) dose-dependently increased both the mean arterial pressure and heart rate. Reproducible pressor effects of H(2)O(2) (1000 nmol) applied consecutively at intervals of 30 min were observed. The pressor effects of intrathecal H(2)O(2) (1000 nmol) were attenuated by pretreatment with intrathecal administration of catalase (500 units), or N-acetyl-cysteine (1000 nmol). The pressor effects of intrathecal H(2)O(2) (1000 nmol) were also antagonized dose-dependently by prior intrathecal injection of AP-5 (DL-2-amino-5- phosphonovaleric acid, 10 and 30 nmol), or 6-cyano-7- nitroquinoxaline-2,3-dione, 10 and 30 nmol. In vitro electrophysiological study in spinal cord slices showed that superfusion of 1 mM H(2)O(2) for 3 min, which had no effect on membrane potential, caused an increase in amplitude of excitatory postsynaptic potentials in SPNs, but had little effect on that of inhibitory postsynaptic potentials. Taken together, these results demonstrated that oxidative stress in spinal cord may cause an increase in spinal sympathetic tone by acting on SPNs, which may contribute to ROS-induced cardiovascular dysfunction.

Ethanol effects on nitric oxide production in cerebral pial cultures.

BACKGROUND: Although alcohol abusers are known to have higher incidences of hemorrhagic cerebrovascular diseases, it is not known whether these changes are associated with ethanol (EtOH) action on nitric oxide (NO) production in the cerebrovascular cells. The purpose of this study was to examine the effects of EtOH treatment on basal and cytokine-induced NO production in cortical pial cultures. METHODS: Cell cultures for this study included murine primary pial vascular cells, primary glial cells and cortical neurons. These cells were exposed to cytokines or EtOH for 24 to 48 hr. The culture media were used for measurement of nitrite, as an indication for NO release, and lactate dehydrogenase (LDH), as an index of cell membrane integrity. In addition, immunocytochemical determinations were carried out to identify cell types and to assess inducible nitric oxide synthase (iNOS). RESULTS: Exposure of primary pial vascular cultures to cytokines that consisted of interleukin-1 beta (IL-1 beta; 250 pg/mL) and interferon-gamma (IFNgamma; 2 ng/mL) or to EtOH (50 to 100 mM) for 24 to 48 hr significantly elevated NO production. NO production could be attenuated by N-nitro-L-arginine (N-arg), a nonspecific NOS inhibitor, or aminoguanidine (AG), an iNOS inhibitor. Increased iNOS immunoreactivity was observed in cytokines- or EtOH-treated pial cells. When pial cells were cocultured with cortical neurons, prolonged EtOH exposure led to a large increase in NO production as well as LDH release. However, this increase was not observed in pial culture alone or in mixed cortical culture. Nevertheless, inhibition of NO production with N-arg or AG did not alter the EtOH-induced LDH release in the pial cells cocultured with cortical neurons. CONCLUSION: These results show that EtOH exposure led to increased production of NO in primary pial cell culture. In mixed culture that contained cortical neurons and pial cells, EtOH induced increase in NO as well as LDH release, which is an indication of loss of cell membrane integrity. However, EtOH-mediated LDH release in mixed cortical pial cultures was not a consequence of the increase in NO production by these cells. Studies that use mixed cortical-pial cultures may provide a unique in vitro system for examining the interactions among glial cells, neurons, and cerebrovascular cells.

Acute exposure to trichloroethylene differentially alters the susceptibility to chemoconvulsants in mice.

The effects of a common industrial solvent, trichloroethylene (TCE), which was once used as an anesthetic agent but its in vivo mechanism is still unknown, on convulsant-induced seizures in mice were examined. Pretreatment with TCE (250-2000 mg/kg, i.p.) significantly increased pentylenetetrazol (PTZ)-, picrotoxin (PIC)-, bicuculline (BIC)-, strychnine (STY)-, 4-aminopyridine (4-AP)- and N-methyl-D-aspartate (NMDA)-induced convulsion thresholds and lethal doses. However, the increase in convulsion thresholds and lethal doses was much greater for GABAergic antagonists (PIC, BIC, and PTZ) than non-GABAergic convulsants (STY, 4AP, and NMDA) following 2000 mg/kg TCE administration. Pre-treatment of mice with disulfiram (an inhibitor of CYP 4502E1) but not 4-methyl pyrazole (an inhibitor of alcohol dehydrogenase) significantly prolonged the time required for TCE (5000 mg/kg, i.p.) to induce the loss of righting reflex. These results suggest that acute exposure to TCE differentially alters the susceptibility to chemically induced convulsions in mice. The anticonvulsive effect of TCE may be predominantly mediated by GABA(A) receptors. In addition, TCE appears to exert a direct anesthetic effect.

Risk factors for pre-eclampsia in an Asian population.

OBJECTIVE: To identify the risk factors for pre-eclampsia in an Asian population. METHOD: We conducted a retrospective cohort study involving 29375 Taiwanese women who delivered between July 1990 and September 1998, excluding pregnancies complicated by chronic hypertension or fetal malformations. RESULT: Four hundred and fifteen women had pre-eclampsia (1.4%). Women who had a history of pre-eclampsia (OR 6.3, 95% CI 4.4, 9.2), multiple gestation (OR 3.6, 95% CI 2.4, 5.5), a prepregnancy BMI > 24.2 kg/m(2) (OR 2.4, 95% CI 1. 8, 3.1), were > 34 years of age (OR 1.8, 95% CI 1.4, 2.4), nulliparous (OR 1.3, 95% CI 1.2, 1.5), had urinary tract infection (OR 4.8, 95% CI 1.5, 15.8), or worked during pregnancy (OR 1.9, 95% CI 1.4, 2.4) were at increased risk of pre-eclampsia. CONCLUSION: Some of the risk factors for pre-eclampsia among Asian women are the same as those of other ethnic groups, whereas some of the risk factors are different.

Arecoline excites rat locus coeruleus neurons by activating the M2-muscarinic receptor.

The action of arecoline on rat locus coeruleus neurons was studied by intracellular recording from the in vitro brain slice preparation. Superfusion of arecoline (0.1-100 microM) caused two dose-related effects, an increased firing rate and, in neurons previously hyperpolarized to a constant potential by passing a steady hyperpolarizing current across the membrane, depolarization. Both effects were associated with a reduction in membrane input resistance. Moreover, the arecoline-induced excitatory effects were antagonized by the muscarinic receptor antagonist, atropine, but not by the nicotinic receptor antagonist, hexamethonium. Methoctramine, a selective M2-muscarinic receptor antagonist, was also effective in reversing the arecoline-induced effects, with a dissociation equilibrium constant of 14.2+/-1.2 nM (n=6). These results therefore suggest that arecoline exerts its excitatory actions by binding to M2-muscarinic receptors on the cell membrane of neurons of the locus coeruleus.

Structure-activity relationships of naturally occurring and synthetic opioid tetrapeptides acting on locus coeruleus neurons.

Intracellular recording was used to study the effects of eight opioid tetrapeptides with similar amino acid sequences, namely endomorphin-1 (Tyr-Pro-Trp-Phe-NH2), endomorphin-2 (Tyr-Pro-Phe-Phe-NH2), morphiceptin (Tyr-Pro-Phe-Pro-NH2), hemorphin-4 (Tyr-Pro-Trp-Thr), Tyr-MIF-1 (Tyr-Pro-Leu-Gly-NH2), Tyr-W-MIF-1 (Tyr-Pro-Trp-Gly-NH2), TAPS (Tyr-D-Arg-Phe-Sar) and DALDA (Tyr-D-Arg-Phe-Lys-NH2), on neurons of the rat locus coeruleus, using a submerged brain slice preparation. All the tetrapeptides inhibited the spontaneous firing of all neurons of the locus coeruleus tested. Higher concentrations also caused hyperpolarization of the neurons and a reduction in input resistance. These inhibitory effects were rapidly and completely reversed by CTAP (D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2, a selective micro-opioid receptor antagonist). The IC50 of the opioid tetrapeptides, in terms of inhibition of spontaneous firing of locus coeruleus neurons, as compared to the concentrations which produced a 5-mV hyperpolarization (HC5 mV) were calculated, giving the same rank order of potency: TAPS (IC50 = 1.9 nM, HC5 mV = 3.4 nM) > endomorphin-1 (IC50 = 8.8 nM, HC5 mV = 22.1 nM) and endomorphin-2 (IC50 = 5.3 nM, HC5 mV = 16.1 nM)> DALDA (IC50 = 20 nM, HC5 mV = 143 nM) > morphiceptin (IC50 = 65 nM, HC5 mV = 335 nM) > Tyr-W-MIF-I (IC50 = 3.8 microM, HC5 mV = 6.7 microM) > hemorphin-4 (IC50 = 6.7 microM, HC5 mV = 36.9 microM) > Tyr-MIF-1 (IC50 = 37.5 microM, HC5 mV = 76.2 microM). Comparison of the ability of endomorphin-1 and endomorphin-2 to inhibit spontaneous firing based on single-cell recordings (n = 5) showed these two peptides to be equipotent. Based on these results, the structure-activity relationships of these opioid tetrapeptides are discussed herein.

Effect of panax notoginseng extracts on inferior sperm motility in vitro.

The purpose of this study was to investigate the effects of Panax notoginseng extracts on inferior sperm motility in vitro. Semen samples were collected from 23 patients with sperm motility between 20% and 40%. The sperm count was over 20 x 10(6)/ml in accordance with the World Health Organization standard. 1.0 mg/ml and 2.0 mg/ml of Panax notoginseng extracts including aqueous extract, n-butanol extract, and polysaccharide fraction on sperm motility and progression were evaluated by computer assisted semen analysis. The results demonstrated that sperm motility as well as progression on inferior sperm motility were enhanced at 1 hour and 2 hours after incubation with all three types of extracts.

Tumor vascular pattern and blood flow impedance in the differential diagnosis of leiomyoma and adenomyosis by color Doppler sonography.

PURPOSE: Our objective was to evaluate the differences between leiomyoma and adenomyosis by color Doppler sonography with new criteria. METHODS: A total of 78 patients with symptomatic uterine nodularities who were sonographically suspected to have leiomyoma or adenomyosis without other coexisting pathologic conditions was enrolled in the study. All patients underwent transvaginal color Doppler sonography (7.0-MHz vaginal probe) or transabdominal color Doppler sonography (5.0 MHz) during the early follicular phase. The morphology, tumor vascular pattern, and blood flow impedance of the uterine tumors were measured. All of the patients underwent surgery and the pathologic reports were used as references. RESULTS: The mean age was not statistically significant in patients with adenomyosis versus leiomyoma (P > 0.05). The morphologic criteria for adenomyosis and leiomyoma by sonography detected 79% of adenomyosis and 84% of leiomyoma. Adenomyosis had 87% randomly scattered vessels or intratumoral signals and 88% of leiomyomas showed peripheral scattered vessels or outer feeding vessels. Eighty-two percent of adenomyosis had a pulsitility index (PI) of arteries within or around uterine tumors > 1.17 and 84% of leiomyomas had a PI < or = 1.17. The reliability test of tumor vascular pattern and blood flow impedance were better than that of using morphological criteria alone. CONCLUSIONS: With the aid of color Doppler sonography, tumor vascular pattern and blood flow impedance of the arteries within or around uterine tumors could more accurately diagnose adenomyosis and leiomyoma in addition to the morphologic criteria on transvaginal sonography.

Acute pentylenetetrazol injection reduces rat GABAA receptor mRNA levels and GABA stimulation of benzodiazepine binding with No effect on benzodiazepine binding site density.

The effects of a single convulsive dose of pentylenetetrazol (PTZ, 45 mg/kg i.p.) on rat brain gamma-aminobutyric acid type A (GABAA) receptors were studied. Selected GABAA receptor subunit mRNAs were measured by Northern blot analysis (with beta-actin mRNA as a standard). Four hours after PTZ, the GABAA receptor gamma2-mRNA was decreased in hippocampus, cerebral cortex, and cerebellum; alpha1-mRNA was decreased in cerebellum; and beta2 subunit mRNA was decreased in cortex and cerebellum. The alpha5 subunit mRNA level was not altered. Those mRNAs that had been reduced were increased in some brain regions at the 24-h time point, and these changes reverted to control levels by 48 h. PTZ effect on GABAA receptors was also studied by autoradiographic binding assay with the benzodiazepine agonist [3H]flunitrazepam (FNP), the GABAA agonist [3H]muscimol, and the benzodiazepine antagonist [3H]flumazenil. There was an overall decrease in [3H]FNP binding 12 but not 24 h after PTZ treatment. In contrast, [3H]muscimol binding was minimally affected, and [3H]flumazenil binding was unchanged after PTZ treatment. Additional binding studies were performed with well-washed cerebral cortical homogenates to minimize the amount of endogenous GABA. There was no PTZ effect on specific [3H]FNP binding. However, there was a significant reduction in the stimulation of [3H]FNP binding by GABA. The results showed that an acute injection of PTZ caused transient changes in GABAA receptor mRNA levels without altering receptor number but affected the coupling mechanism between the GABA and benzodiazepine sites of the GABAA receptor.

Risk factors for placenta accreta.

OBJECTIVE: To identify risk factors associated with placenta accreta in a large cohort study. METHODS: Data for this study came from the Taiwan Down Syndrome Screening Group, an ongoing project on feasibility of serum screening in an Asian population. Women who had serum screening for Down syndrome at 14-22 weeks' gestation using alpha-fetoprotein (AFP) and free beta-hCG between January 1994 and June 1997, and delivered in the same institution, were included (n = 10,672). Those who had multiple gestations (n = 200), overt diabetes (n = 11), or fetal malformations (n = 101) were excluded. If a woman was involved more than once, one randomly selected pregnancy was included in the analysis (n = 9349). Twenty-eight pregnancies were complicated by placenta accreta, diagnosed by clinical presentation (n = 26) or histologic confirmation (n = 2). Multiple logistic regression with adjustment for potentially confounding variables was used to identify independent risk factors for placenta accreta. RESULTS: Women who had placenta previa (odds ratio [OR] 54.2; 95% confidence interval [CI] 17.8, 165.5) and second-trimester serum levels of AFP and free beta-hCG greater than 2.5 multiples of the median (OR 8.3; 95% CI 1.8, 39.3 and OR 3.9; 95% CI 1.5, 9.9, respectively), and were 35 years and older (OR 3.2; 95% CI 1.1, 9.4) were at increased risk of having placenta accreta. CONCLUSION: Risk factors for placenta accreta include placenta previa, abnormally elevated second-trimester AFP and free beta-hCG levels, and advanced maternal age.

Activation of rat locus coeruleus neuron GABA(A) receptors by propofol and its potentiation by pentobarbital or alphaxalone.

The action of propofol on the rat locus coeruleus was examined using intracellular recording from in vitro brain slice preparations. Concentrations of propofol between 3 and 300 microM were tested. At 100 microM, propofol completely inhibited the firing of all neurons tested (n=34); this was associated with a 5.7-mV hyperpolarization (range 0-16 mV, n=33) and a 35.6% reduction in input resistance (range 7.3-66.1%, n=33). The propofol-induced responses were not affected by 2-hydroxysaclofen (50 microM) or BaCl(2) (300 microM), but were completely blocked by bicuculline methiodide (100 microM) or picrotoxin (100 microM), indicating that propofol acts on GABA(A) receptors. As assessed by inhibition of the spontaneous firing rate, propofol was 5.6-fold more potent than GABA (gamma-aminobutyric acid). Potentiation of the propofol effect by other general anesthetics or other drugs was also investigated. When pentobarbital (100 microM) was tested alone on locus coeruleus cells, no change in membrane potential or input resistance was seen and there was only a 20.3+/-7.2% (n=8) inhibition of firing rate; however, in combination with 30 microM propofol, it caused a 6.1-fold greater increase in membrane hyperpolarization and a 9.7-fold greater reduction in input resistance than 30 microM propofol alone. A relatively low concentration of alphaxalone (10 microM), when tested alone, had little effect on the membrane potential or input resistance and only produced a 46.0+/-8.9% (n=8) inhibition of firing rate; however, in combination with 30 microM propofol, it caused a 9.3-fold greater hyperpolarization and an 8.6-fold greater reduction in input resistance compared with 30 microM propofol alone. In contrast, diazepam caused no potentiation of either propofol- or GABA-induced responses. Our data also indicate that locus coeruleus neuron GABA(A) receptors possess distinctive pharmacologic characteristics, such as blocking of the propofol effects by zinc and insensitivity to diazepam and the direct action of pentobarbital. On the basis of these pharmacologic properties, we suggest that locus coeruleus neuron GABA(A) receptors do not contain the gamma subunit.

Decreased benzodiazepine binding with little effect on gamma-aminobutyric acid binding in rat brain after treatment with antisense oligodeoxynucleotide to the gamma-aminobutyric acidA receptor gamma-2 subunit.

Benzodiazepine potentiation of gamma-aminobutyric acid (GABA) neurotransmission is associated with the presence of a gamma-2 subunit in the GABAA receptor. A method was developed to modify the gamma-2 subunit expression in adult rat brain. Unilateral intracerebroventricular (i.c.v.) infusion of a 17-base phosphorothioate-modified antisense oligodeoxynucleotide (ASO) was performed every 12 hr for 3 days. Controls were treated with a sense oligodeoxynucleotide. Parasagittal brain sections were used for quantitative autoradiographic analysis of radioligand binding. ASO treatment caused a 15% to 25% decrease of specific [3H]flunitrazepam binding in most brain areas, with statistically significant decreases in frontal cortex, cerebellar molecular layer, zona reticulata of substantia nigra and CA3 of hippocampus. In contrast, [3H]muscimol binding was not changed. [3H]GABA binding was also unchanged, except for a 10% decrease in cerebellar granule cell layer. The effect on the chloride channel of the GABAA receptor complex was examined by 4'-ethynyl-4-n-[2, 3-3H2]propylbicycloorthobenzoate binding; most brain areas showed small decreases in 4'-ethynyl-4-n-[2, 3-3H2]propylbicycloorthobenzoate binding. However, hippocampal regions showed much larger decreases. Binding of the adenosine A1 receptor antagonist [3H]8-cyclopentyl-1,3-dipropylxanthine was used to examine possible secondary effects of the ASO. There was a decrease in [3H]8-cyclopentyl-1,3-dipropylxanthine binding, but this was much smaller than the change in [3H]flunitrazepam binding, and no area showed a significant effect. Quantitative immunoblotting with a monoclonal antibody that recognizes GABAA receptor beta-2 and beta-3 subunits showed no change in immunoreactivity in cerebellar tissue after ASO treatment. The results indicate a selective effect on benzodiazepine binding to GABAA receptors and a possible change in receptor subunit composition.

Primary hyperparathyroidism in pregnancy--report of 3 cases.

Three cases of primary hyperparathyroidism in pregnancy are described. Patient 1 developed left thigh pain and lower abdominal pain at 34 weeks' gestation. Patient 2 had right flank pain and lower abdominal pain at 32 weeks' gestation. Both patients accepted medical therapy initially, which resulted in poor control of hypercalcemia. Patient 1 delayed her parathyroidectomy until the postpartum period; she had maternal hypercalcemia and neonatal hypocalcemia. Patient 2 accepted parathyroidectomy at 32 weeks' gestation with an uneventful outcome for both mother and baby. Patient 3 was asymptomatic; her hyperparathyroidism was diagnosed postpartum after neonatal hypocalcemia and agreed to parathyroidectomy. All 3 patients had a parathyroid adenoma.