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Purpose: Abnormal spindle-like microcephaly associated (ASPM) plays an important role in neurogenesis and cell proliferation. This study is to elucidate its role in hepatocellular carcinoma (HCC), particularly early tumor recurrence (ETR) and prognosis., Experimental Design: We used reverse transcription-PCR assays to measure the ASPM mRNA levels in 247 HCC and correlated with clinicopathologic and molecular features., Results: ASPM mRNA levels were high in fetal tissues but very low in most adult tissues. ASPM mRNA was overexpressed in 162 HCC (66%) but not in benign liver tumors. ASPM overexpression correlated with high alpha-fetoprotein (P = 1 x 10(-8)), high-grade (grade II-IV) HCC (P = 2 x 10(-6)), high-stage (stage IIIA-IV) HCC (P = 1 x 10(-8)), and importantly ETR (P = 1 x 10(-8)). ETR is the most critical unfavorable clinical prognostic factor. Among the various independent histopathologic (tumor size, tumor grade and tumor stage) and molecular factors (p53 mutation, high alpha-fetoprotein, and ASPM overexpression), tumor stage was the most crucial histologic factor (odds ratio, 14.7; 95% confidence interval, 6.65-33.0; P = 1 x 10(-8)), whereas ASPM overexpression (odds ratio, 6.49; P = 1 x 10(-8)) is the most important molecular factor associated with ETR. ASPM overexpression was associated with vascular invasion and ETR in both p53-mutated (all P values = 1 x 10(-8)) and non-p53-mutated HCC (P = 1 x 10(-8) and 0.00088, respectively). Hence, patients with APSM-overexpressing HCC had lower 5-year survival (P = 0.000001) in both p53-mutated (P = 0.00008) and non-p53-mutated HCC (P = 0.0027). In low-stage (stage II) HCC, ASPM overexpression also correlated with higher ETR (P = 0.008)., Conclusion: ASPM overexpression is a molecular marker predicting enhanced invasive/metastatic potential of HCC, higher risk of ETR regardless of p53 mutation status and tumor stage, and hence poor prognosis.

Aims: The purpose of this study was to compare the effectiveness between ice towel (moist cryotherapy) and ice-pack (dry cryotherapy) in postoperative care., Background: Orthognathic surgery is often performed to modify the facial appearance of individuals. Cryotherapy was used to reduce the postoperative discomfort, such as local heat, pain and swelling. However, studies to compare the difference in effectiveness between moist and dry cryotherapy are lacking., Design: A quasi-experimental design with follow-ups at regular intervals was conducted. The study involved data collection at the preoperative, postoperative 60, 90, 120, 180 minutes, 24 hours and 48 hours., Methods: Subjects were recruited and assigned to group I (n = 27) and group II (n = 21) by locations. Group I received ice towels whereas group II used ice-packs as a strategy to reduce postoperative discomfort. Subjective indicators of local heat, pain and swelling were measured on postoperative days 1 and 2. When subjects went to postoperative recovery room, local temperatures on both sides of four facial areas and forehead were measured and repeated at scheduled intervals., Results: Both subjective and objective indicators changed during the research period in these two groups. Group I subjects reported less postoperative discomfort, such as heat, swelling and pain. Group II subjects had higher reduction of local temperature in certain areas within 180 minutes., Conclusions: Both moist- and dry cryotherapy reduced postoperative discomfort effectively. The moist cryotherapy was more effective in reducing subjective discomfort caused by the operation. The dry cryotherapy reduced local temperature more effectively in certain areas after surgery., Relevance to Clinical Practice: Cryotherapy could reduce postoperative discomfort, such as local heat, pain and swelling. When patient comfort is the major outcome of nursing intervention, moist cryotherapy is strongly suggested.

Poisoning is one of the most common reasons for visiting the emergency department in many countries, and the pattern varies from countries to countries and time to time. To compare the etiology and outcome of poisoning patients in different gender and age groups, we conducted a prospective study at the emergency departments of two medical centers in southern Taiwan between January 2001 and December 2002. All cases of poisoning, excluding patients diagnosed as cases of alcohol or food poisoning, were included, and relevant information was collected. There were 1512 cases of poisoning observed with a male to female ratio of 1:1.2 (684/828). Overall, drugs (49.9%) were the main agents involved, and a suicidal attempt (66.1%) was the predominant etiology. A total of 63 fatalities (4.2%) were observed and pesticides, especially paraquat, resulted in most fatalities. Patients aged 19-30 years constituted the most cases, and significant differences in exposure agents, causes, and fatality rates were found among different age and gender groups. The results are compatible with the trend reported by other Asian countries. This study also shows important differences existing in poisoning patients of different age and gender groups. Therefore, different poisoning-prevention strategies should be applied to different groups.

We observe the stabilization of a single-(double-) charge optical vortex propagating in a self-focusing medium. The optical vortex, which carries a phase singularity at its center, usually breaks up in a self-focusing medium due to the so-called azimuthal instability. However, by adding a small rotating azimuthally-periodic intensity modulation on the vortex light beam, which propagates in a noninstantaneous self-focusing medium, we successfully suppress the azimuthal instability. This observation is confirmed by both numerical simulation and perturbational analysis.

Salivary gland tumors are uncommon and most reported series include tumors affecting both major and minor glands. Very few series have focused solely on intra-oral minor salivary gland tumors. The aim of this study is to report the clinicopathological data of intra-oral minor salivary gland tumors in our oral biopsy files during the last 14 years. A total of 546 minor salivary gland tumors, including 305 benign (55.9%) and 241 malignant (44.1%) lesions, were reviewed. The two most common tumors were pleomorphic adenoma (181 cases, 33.2%) and mucoepidermoid carcinoma (125 cases, 22.9%), and the most commonly affected site was the palate (181 cases, 33.2%). The highest incidence was found in patients in the 5-7th decade of life, and females were more commonly affected than males in the vast majority of various histological types of tumors. Large series of intra-oral minor salivary gland tumors help to understand their clinical and pathological aspects and consequently their proper management and prognosis.

Objectives: We evaluated the effects of uvulopalatopharyngoplasty (UPPP) on the work of breathing (WOB) in obstructive sleep apnea syndrome (OSAS)., Methods: Fifteen healthy subjects and 30 subjects with OSAS who desired UPPP were prospectively enrolled. All underwent measurement of WOB while awake as well as in a sleep study. These studies were repeated 3 months after UPPP in the patients with OSAS., Results: In OSAS before UPPP, the WOB while supine was increased above that of normal subjects. After UPPP, the WOB while supine remained elevated in those whose OSAS did not respond to surgery, and it returned to normal levels in patients whose OSAS improved after UPPP., Conclusions: Abnormal WOB in patients with OSAS returns to normal if UPPP results in amelioration of OSAS.

Leiomyoma usually originates from the uterus and alimentary tract, but rarely from the soft tissue of the head and neck. It is extremely rare that leiomyoma appears in the external auditory canal. A 47-year-old male with left external auditory canal leiomyoma presented with conductive hearing impairment and post-auricular swelling. Tumor excision was successful via a retroauricular approach. The pathological examination demonstrated a vascular leiomyoma without malignant change. To date, including our case, only three cases of external auditory canal leiomyoma have been reported. The tumor occurs mainly in adult males aged around 50 and should be included in the differential diagnoses for external auditory canal tumor. The proper treatment of choice is complete excision. In case of an external auditory canal tumor, even if it is believed to be benign before surgery, precise pathologic examination is required to exclude the possibility of malignancy.

To compare the difference between primary proximal renal tubular acidosis (PRTA) and Fanconi syndrome (FS), and to find out possible risk factors for growth retardation, we studied the long-term growth, clinical, laboratory, and radiological findings associated with the treatment of six children with primary FS and 15 children with PRTA. The ages of the children with FS were much older than those with PRTA at initial diagnosis (7.03+/-3.82 vs. 1.63+/-1.56 years). The height standard deviation score (SDS) at the start of treatment was significantly lower in FS than in PRTA. Catch-up growth was noted in PRTA at the end of follow-up (initial height SDS -2.13+/-1.10 vs. last height SDS -1.33+/-1.43, P=0.023 by paired t-test), whereas apparent linear growth impairment was found in FS in terms of overall growth velocity index (82.70+/-8.37%) and height SDS (initial -3.25+/-0.95 vs. last -3.15+/-0.31, P=0.791). There was also a higher rate of rickets occurrence in FS (3/6 vs. 0/15 in PRTA). Hypophosphatemia during the follow-up period was more frequent for FS than PRTA (69.2+/-26.1% vs. 7.0+/-25.8%, P<0.001), whereas metabolic acidosis (blood HCO(3)<20 mmol/l) was less efficiently corrected in PRTA (49.1+/-20.5% vs. 25.2+/-21.6% in FS, P=0.028). Moreover, the height Delta SDS correlated well with the mean serum P level during the treatment period in these patients (R=0.528, P=0.014 for all children; R=0.917, P=0.01 for FS patients). Our data suggest that metabolic acidosis may not be the sole factor causing growth impairment in FS. Correction of metabolic acidosis may indeed improve growth in PRTA but not in FS. This study indicates that factors other than metabolic acidosis, such as phosphate depletion and delayed diagnosis/treatment, should be considered to be important causes of growth retardation in FS.

Central mucoepidermoid carcinoma (MEC) is an entity whose origin is still controversial. Glandular odontogenic cyst (GOC) is a recently described lesion whose relationship to low-grade central MEC has been reported in the literature. Our aim was to assess the cytokeratin (CK) profile of central MEC and GOC, and compare the results with CK expression in salivary gland MEC and odontogenic cysts and tumors. Eighty-five cases, including 6 central MECs, 23 salivary gland MECs, 10 GOCs, 34 odontogenic cysts and 12 ameloblastomas, were studied through immunohistochemistry using eleven monoclonal anti-CK antibodies. All central MECs expressed CKs 5, 7, 8, 14, and 18 and all GOCs expressed CKs 5, 7, 8, 13, 14, and 19. Comparing CK expression from GOC and central MEC we found differences in CKs 18 (30% vs 100%) and 19 (100% vs 50%). Central MEC and GOC are probably distinct entities with CK profiles similar to lesions of glandular and odontogenic origins, respectively, and expression of CKs 18 and 19 could be useful in their differential diagnosis.

Hyalinizing clear cell carcinoma (HCCC) of the salivary gland is new disease only recognized in recent years. It is rare and the standard treatment is still under investigation. This is a report of a 42-year-old female with HCCC who presented with a painless submucosal hard palatal mass of three years duration. Wide excision of the tumour and the underlying palatal and maxillary bones was performed. Pathological examination revealed typical clear cells arranged in anastomosing trabeculae, cords, nests, or solid sheets with a hyalinizing stroma. These clear cells were positive for the periodic acid-Schiff (PAS) reaction but were negative for the mucin stain. Immunohistochemically, these neoplastic cells were positive for cytokeratin, but negative for actin. No recurrence nor distant metastasis was found during the eight-month follow-up period.

Background: Correct identification of acute lobar nephronia (ALN) is necessary to prevent progression to renal abscess. The goal of this retrospective study was to determine whether the sonographic finding of severe nephromegaly (i.e. renal length greater than mean + 3 sd) is a preselection criterion for computed tomographic (CT) scanning in diagnosing pediatric ALN among children with an acute upper urinary tract infection., Design/methods: We evaluated a new imaging work-up scheme to detect pediatric ALN. All patients with urinary tract infection were evaluated with ultrasonography. If a markedly enlarged kidney or focal mass was present sonographically, CT scanning was done immediately. CT scanning was also performed when the patient had borderline nephromegaly and remained febrile for 72 h after start of antibiotic treatment. ALN diagnosis was made on the basis of positive CT findings., Results: Thirty patients with ALN (13 left, 7 right, 10 bilateral) and one with acute pyelonephritis were identified. ALN in all patients resolved after 3 weeks of antibiotic treatment. Thirty-nine of the 62 kidneys evaluated showed severe nephromegaly, and 10 had focal renal masses. With CT diagnosis of ALN as the reference standard, the sensitivity of severe nephromegaly was 90.0% and the specificity was 86.4%. When the focal renal mass was added as a combining predictor, the sensitivity further increased to 95%., Conclusions: Pediatric ALN was effectively predicted using sonographic findings of severe nephromegaly and/or focal mass before CT scanning.

Objective: A retrospective study was conducted to investigate the anatomic location and characteristics of amyloid deposition in the oral cavity., Study Design: Seventeen biopsy specimens that were conclusive for a diagnosis of amyloidosis were assessed in terms of their anatomic location and histopathologic characteristics., Results: Biopsy specimens were received from 13 patients-9 females and 4 males. Six specimens were taken from the buccal mucosa, 4 from the tongue, 3 from the palate, 2 from the gingiva, and 2 from the floor of the mouth. Fifteen of 17 specimens (88%) had amyloid deposition in the subepithelial connective tissue in all locations., Conclusion: On the basis of our pilot data, a previously overlooked intraoral anatomic location, the buccal mucosa, may prove to be of higher diagnostic value than others previously reported in terms of obtaining a diagnosis of amyloidosis. In addition, the manner in which tissue biopsies are conducted for amyloid detection may be altered to create less morbidity.

To initiate the use of a tertiary multileaf collimator (MLC) in the clinic, a set of dosimetry data for clinical use of the MLC, the secondary field size jaw and the MLC tracked by the jaw were measured. The dose calculation technique from the commissioned jaw field data was established. The dosimetry characteristics included absolute output (Dw), collimator scatter factor (Sc), total scatter factor (Scp), phantom scatter factor (Sp), percentage depth dose (PDD), tissue-maximum ratio (TMR), and peak scatter factor (PSF). The absolute output of the MLC field was +5% to +2% greater than that of the same jaw size field from 4 x 4 to 24 x 24 cm2 fields. The variation of Sc and Scp ranged from 4 x 4 to 24 x 24 cm2 fields and were less than that of the jaw fields, while the Sp, PDD and TMR values remained the same. Importantly, when the MLC-only field was performed without the collimator jaws tracking close to the field segments, greater output was delivered, and PSFs should be used to calculate the MLC field output.

The androgen receptor (AR) is a member of the nuclear receptor (NR) superfamily that mediates the effects of androgens on target tissues. Over the last decade, it has become apparent that NRs require accessory factors for optimal activation of target gene expression. Numerous NR coregulators have been identified, with diverse structures and potential mechanisms of coregulation, creating an increasingly complicated picture of NR action. Due to the expanding complexity of the coregulator field, this review will focus on the AR ligand-binding domain (LBD) and N-terminal interacting proteins identified by our lab. The LBD-interacting proteins ARA70, ARA55 and ARA54 were first characterized and ARA70 was found to have a relatively higher specificity for the AR in human prostate cancer DU145 cells. Characterization of the functional relationship between the AR and these coregulators indicated that ARA70 and ARA55 could enhance the androgenic effects of 17beta-estradiol (E2) and hydroxyflutamide (HF), an antiandrogen commonly used in the treatment of prostate cancer. ARA160, an AR N-terminal interacting protein also known as TATA element modulatory factor (TMF), was subsequently shown to cooperate with ARA70 in enhancing AR activity. Another AR N-terminal interacting protein, ARA24, interacted with the poly-Q tract, a region within the N-terminus of the AR linked to Kennedy's disease (X-linked spinal and bulbar muscular atrophy). More recently, our lab has identified ARA267, a SET domain containing protein, and supervillin, an F-actin binding protein, as AR coregulators. Collectively, the data from these studies indicate that these coregulators are necessary for optimal AR transactivation. Interruption of the interaction between AR and these proteins may serve as a new therapeutic target in the treatment of prostate cancer.

We recently developed a new method for simple determination of particle magnetic susceptibility using analytical magnetapheresis. This new method does not require laborious calibration plots and trial susceptibility values as do previous analytical magnetapheresis methods. The new method is based on balancing channel flow rates and magnetically induced flow rates for particle deposition in analytical magnetapheresis. The maximal flow rate for complete particle deposition was determined experimentally and set to equal the magnetically induced flow rate for determining particle magnetic susceptibility. This magnetic susceptibility determination generally takes less than 20 min. Several magnetically susceptible and ion-labeled particles were tested using this new method. The carrier magnetic susceptibilities were varied, and erbium ion-labeled particles were studied experimentally, resulting in successful susceptibility determinations of erbium ion-labeled particles and yeasts. The precision of each measurement was generally approximately 10%. Experimental determination of particle magnetic susceptibilities differed by less than 10% from reference measurements taken using a superconducting quantum interference device magnetometer. This method can determine minimal susceptibilities on the order of 10(-9) cgs. The minimum number of erbium labeling ions per particle required for complete deposition of silicas and yeasts was found to be 6.7 x 10(9). Analytical magnetapheresis shows good potential for use in simple determination of particle magnetic susceptibilities and should become a useful technique.

Structure-anorectic activity relationship of two substituted amphetamines has been investigated in this study. Literature reports showed conflicting results in their anorectic activities in spite of the similarity in chemical structures of metaraminol and phenylephrine. Hence, the effects of alpha-carbon atom substitution and primary (metaraminol) and secondary amine (phenylephrine) moieties of these substituted amphetamines on the anorexia of rats were investigated in this study in nonfood- and food-deprived rats. Food intake at 1, 3, 14, and 24 h intervals, water intake at a 24-h interval, and body weight alteration for 10 days were monitored after daily drug administration for 3 consecutive days. Both metaraminol and phenylephrine were found to be potent anorectic. The relative anorectic potencies of phenylephrine were 0.54 and 0.81 of that of metaraminol at 1- and 3-h intervals, respectively. Body weight of rats treated with metaraminol (5.0 mg/kg) and phenylephrine (10 mg/kg) decreased significantly from Days 1 to 9.

This study investigated the effects of chlorpheniramine (CPA, 10-25 mg/kg), diphenhydramine (DIPH, 20 mg/kg), tripelennamine (TRIP, 20 mg/kg), and pyrilamine (PYRI, 20 mg/kg) on 3, 4-methylenedioxymethamphetamine (MDMA, 20 mg/kg x 2)-induced hyperthermia and depletion of indoles in rat brains, on the uptake of serotonin and dopamine into rat synaptosomes, on the binding affinity of CPA for biogenic amine transporters in the synaptosomes of rat brain, and on the scavenging hydroxyl free radicals activity. Rats were treated with two injections of MDMA, CPA, DIPH, TRIP, PYRI, and saline, alone or in combination of MDMA with one of the antihistamines, 6 h apart and sacrificed 5 days later. Rectal temperature was measured prior to and hourly following the drug injections for 13 h. As compared to saline controls, MDMA increased body temperature and decreased levels of indoles, measured by HPLC, in several brain regions of rats. CPA attenuated and DIPH had no effect on MDMA-induced hyperthermia, yet both attenuated the depletion of indoles, whereas PYRI and TRIP potentiated these effects. CPA inhibited the binding of [(3)H]paroxetine and [(3)H]nisoxetine to the synaptosomes of cerebral cortex and of [(3)H]win 35,428 to the synaptosomes of striatum. CPA, DIPH, TRIP, and PYRI inhibited [(3)H]serotonin uptake. CPA, PYRI, and TRIP, but not DIPH, scavenge hydroxyl radicals. Possible mechanisms of the different effects of the antihistamines on MDMA-induced hyperthermia and depletion of serotonin are discussed. Published 1999 Wiley-Liss, Inc.

Various effects of chlorpheniramine (CPA), diphenhydramine (DIPH), tripelennamine (TRIP), and pyrilamine (PYRI) on fenfluramine (FEN)-induced depletion of serotonin in the brain of rats were observed to be dependent on body temperature. Levels of 5-HT and 5-HIAA in the frontal cortex, hippocampus, and striatum of rats treated with FEN (10 mg/kg, once or twice daily x 4 days) decreased to approximately 30% (P < 0.01) that of controls with no significant changes after CPA, DIPH, TRIP, and PYRI. Treatment with FEN plus CPA (5, 10, 20 mg/kg) and FEN plus DIPH (20 mg/kg), but not FEN plus TRIP (20 mg/kg) and FEN plus PYRI (20 mg/kg), increased brain serotonin levels 2- to 3-fold more than those treated with FEN plus saline. Treatment with FEN plus CPA and FEN plus DIPH, but not FEN plus TRIP and FEN plus PYRI, decreased rectal temperature with no significant change after FEN. The antihistamines alone decreased temperature at a 1-hour period and enhanced FEN-induced reduction in body weight. Possible mechanisms of the different effects of antihistamines on FEN-induced depletion of serotonin are discussed.

The present study examined the effect of N-tert-butyl-alpha-phenylnitrone (PBN) on 3,4-methylenedioxmathamphetamine (MDMA)-induced depletion of serotonin in the CNS. Rats were treated with two concurrent injections of MDMA (20 mg/kg, s.c.), PBN (50-400 mg/kg dissolved in ethanol, 50 mg/ml of 25% ethanol, i.p.), saline or 25% ethanol, alone or in combination, 6 h apart, and sacrificed 5 days later. Rectal temperature was measured prior to and hourly following the drug injection for 5 h. Monoamine levels in the tissue were measured by HPLC. Density of the 5-HT transporters was assayed by [3H]paroxetine binding. Rectal temperature of rats increased after MDMA, decreased after PBN, ethanol, PBN plus ethanol, and MDMA plus ethanol, and was not significantly altered after MDMA plus PBN. Levels of 5-HT and 5-HIAA in the frontal cortex, hippocampus, striatum, and brain stem of rats decreased significantly after MDMA or MDMA plus ethanol, but not after MDMA plus PBN, PBN plus ethanol (PBN dissolved in ethanol), or ethanol as compared to the saline controls. Levels of 5-HT and 5-HIAA in the brain tissues of rats treated with MDMA plus PBN were elevated as compared to those treated with MDMA plus saline. Similar results were observed in the density of 5-HT transporters in the frontal cortex and hippocampus. These results indicate that scavenging of free radicals of MDMA metabolites or reactive oxygen species by PBN and with lowering of body temperature protected against MDMA-induced depletion of serotonin transmitter.

The drug 3,4-methylenedioxymethamphetamine (MDMA) is a serotonergic neurotoxicant that causes hyperthermia and depletion of serotonin (5-HT) and 5-hydroxy-indole-3-acetic acid (5-HIAA) in the central nervous system. Formation of neurotoxic metabolites of MDMA, e.g., 2,4,5-trihydroxy-methamphetamine and 2,4,5-trihydroxyamphetamine, involves hydroxyl and/or superoxide free radicals. The present study was designed to determine whether the hydroxyl free-radical-trapping agent salicylate could provide protection against MDMA neurotoxicity in rats. In the acute studies, sodium salicylate (12.5-400 mg/kg, calculated as free acid) was injected interperitoneally (i.p.) 1 h before subcutaneous (s.c.) injections of MDMA (20 mg/kg as base). In the chronic studies, sodium salicylate (3.1-100 mg/kg) was injected i.p. 1 h before repeated s.c. injections of MDMA (10 mg/kg as base, twice daily, at 0830 and 1730 h for 4 consecutive days). Repeated MDMA administration depleted contents of 5-HT and 5-HIAA in the frontal cortex, hippocampus and striatum. Coadministration of salicylate plus MDMA did not significantly alter MDMA-induced depletion of 5-HT and 5-HIAA in these tissues. Thus, salicylate, a hydroxyl free-radical-trapping agent, does not protect against MDMA-induced hyperthermia and depletion of 5-HT and 5-HIAA. These observations suggest that MDMA-induced neurotoxicity may occur mainly through the production of superoxide or other radicals rather than hydroxyl free radicals. Salicylate actually potentiated MDMA-induced hyperthermia and lethality, findings that might be of clinical relevance.

Androgen and androgen receptor (AR) play an important role in sexual differentiation and prostate proliferation. To investigate AR gene transcriptional regulation, a 2.3-kilobase AR gene promoter region was isolated, sequenced, and characterized. Chloramphenicol acetyltransferase (CAT) assay and sequence homology search of AR gene promoter among human, rat, and mouse revealed some potential cis-acting elements, including a GC box, a suppressor region, and a purine-rich element. Deletion analysis and gel retardation assay using a 50-base pair (bp) double-strand purine-rich element showed that this purine-rich element can bind to specific proteins in nuclear extract of LNCaP and HeLa cells and may be essential for AR gene transcription. Furthermore, to investigate the effect of cAMP on AR gene transcription, we treated LNCaP and HeLa cells with 10 mM (Bu)2cAMP after transfection with CAT gene reporter plasmids linked to the AR gene promoter. This treatment induced several folds of CAT activity in LNCaP cells only, and the induction was further confirmed at AR mRNA level by Northern blot analysis and reverse transcription-polymerase chain reaction assay. Deletion analysis of the AR gene promoter showed that a region between 530 bp and 380 bp upstream of AR gene transcription initiation site, which includes one potential cAMP response element (CRE), is responsible for cAMP induction. Gel retardation analysis using this CRE (AR/CRE1) showed that AR/CRE1 can bind to specific proteins in nuclear extract of LNCaP cells, which appears to form a different binding complex compared to somatostatin/CRE.

A case-control study was carried out in 59 patients with newly diagnosed hepatocellular carcinoma and 101 control subjects, who were all male hepatitis B carriers. The odds ratios of hepatocellular carcinoma occurring among hepatitis B carriers in the lowest quartile and those highest quartile of dietary and serum status were 5.3 (1.9 to 15.0) and 86.9 (20.0 to 377.2), respectively. The odds ratios for hepatitis B carriers in the lowest quartile and those in the highest quartile of dietary and serum beta-carotene status were 1.7 (0.7 to 4.1) and 5.0 (1.9 to 13.2). Vitamin E status did not differ in case patients and control subjects. Low education level, heavy consumption of alcohol, and smoking status were also associated with increased odds of hepatocellular carcinoma. Serum retinol, positively associated with dietary retinol, demonstrated an independent effect on hepatocellular carcinoma. This effect may reflect changes in the physiologic condition of the patients at the time of entering the hospital.

Chlamydia is a sexually transmitted disease of epidemic proportions, infecting an estimated 4 million people a year. It results not only in infertility and ectopic pregnancy but also in infant morbidity and mortality. Ectopic pregnancy is responsible for 11 percent of maternal deaths. About 60 percent of infected women can transmit the bacteria at birth to their infants. Early detection and treatment of chlamydia in both men and women, especially prenatal women, is critical. Chlamydia trachomatis infection of the cervix was found in 8.1 percent of a group of 1,004 pregnant women at a hospital prenatal clinic by means of a direct fluorescent antibody test. The prevalence of C. trachomatis was only 0.7 percent in 277 pregnant women receiving prenatal care from private practitioners. All patients between 27 and 30 weeks gestation who tested positive were treated with oral erythromycin. Their partners were treated with tetracycline. The outcome of pregnancy in patients treated for chlamydial infection was compared with a control group of noninfected mothers from the same population. The frequency of premature rupture of the membranes, prematurity, and low Apgar scores among the treated women were not significantly different from those in the control group. There was a significant difference, however, between the two groups in the incidence of low mean birth weight infants and the presence of meconium. Children can acquire a chlamydial infection at birth from contact with infected cervico-vaginal secretions. If not detected and treated, these infected infants may develop conjunctivitis, bronchiolitis, and pneumonia. It is suggested, therefore, that all patients at prenatal clinics be screened for chlamydial cervicitis. Those testing positive and their partners should be treated.

Volunteers were injected im with 100 mg of tripelennamine (pyribenzamine).HCl dissolved in saline. Timed urine was collected. Tripelennamine and its metabolites were identified by GC/MS. Amounts of free tripelennamine excreted in the 0-2-, 2-4-, 4-8-, 8-12-, and 12-24-h urine samples were found to be 0.30, 0.56, 0.17, 0.21, and 0.0%, respectively, of the administered dose. In the same time periods, total tripelennamine (free plus conjugated) amounts were found to be 0.92, 1.20, 0.96, 1.30, and 1.31%, respectively, and total amounts 2-[alpha-hydroxybenzyl(2-dimethylaminoethyl)amino]pyridine(alpha- hydroxytripelennamine) plus an unidentified metabolite were found to be 0.16, 3.35, 3.06, 7.46, and 8.85% of the dose, respectively.

Rats were injected SC with a dose of 10 mg/kg (as base) of 3,4-methylenedioxyamphetamine (MDA), or 3,4-methylenedioxymethamphetamine (MDMA), 4-hydroxy-3-methoxyamphetamine, alpha-methyldopamine and alpha-methylnorepinephrine, metabolites of MDA, and alpha-methylepinephrine, a putative metabolite of MDMA, twice daily for either 5 or 7 consecutive doses. The rats were killed 24 h after the last injection and monoamines in discrete brain regions were assayed. MDA, MDMA, 4-hydroxy-3-methoxyamphetamine and alpha-methyldopamine, but not alpha-methylepinephrine, decreased the concentration of serotonin (5-HT) in the frontal cortex. MDA and MDMA, but not 4-hydroxy-3-methoxyamphetamine, alpha-methyldopamine and alpha-methylepinephrine, also decreased the concentration of 5-hydroxyindoleacetic acid (5-HIAA) in the frontal cortexes. In stimulatory studies, MDA and MDMA, but not their metabolites except alpha-methylepinephrine, which increased activity at 15 and 30 min, increased locomotor activity from 15 to 180 min following the drug administration.

Rats were injected SC or IP with a dose of cocaine at 20 mg/kg twice daily or saline (2 ml/kg) for 15 consecutive doses. Horizontal (including ambulatory and repetitive activity) and ambulatory locomotor activities were assessed following the first (acute) and the 15th (chronic) injections. Total locomotor activity (area under curve, AUC) following the acute and the chronic administration of cocaine were comparable, regardless of the route of drug administration. However, the temporal patterns of activity were significantly different; the peak of locomotor activity occurred earlier (chronic vs. acute, 20 vs. 40 min after IP; 130 vs. 180 min after SC) following chronic cocaine administration. Furthermore, the peak activity was significantly higher (3-fold after IP and 50% after SC) in chronically than in acutely treated rats, providing evidence for sensitization. In contrast, activity in the late session (240-280 min after SC) was significantly lower following the chronic SC cocaine administration, providing evidence for desensitization. The absolute slope values of the ascending phase and the descending phase were significantly larger following chronic administration of cocaine than that following the acute dosing. The possibility of changes in locomotor activity with alteration of pharmacokinetics on chronic cocaine treatment is discussed.

Rats were injected with cocaine (20 mg/kg, s.c. or i.p. twice daily for 8 days) or saline and killed at 1, 8, 15 or 48 days after the last injection. The concentrations of norepinephrine (NE), dopamine (DA), serotonin (5-HT) and their metabolites, assayed by HPLC-EC, in frontal cortex, hippocampus, striatum, hypothalamus, midbrain, pons-medulla and spinal cord were not significantly different from those in the saline-injected controls at any of the time points examined. These data suggest that the repeated cocaine administration in rats does not produce any long-term depletion in brain catecholamine and 5-HT content suggesting no neurotoxic effects of the drug.

N-(2-Dimethylaminoethyl)benzylamine and 2-benzylaminopyridine were identified as two new urinary metabolites of tripelennamine in the rat by GC/MS. 2-(4-Methoxybenzylamino)-pyridine and N-(dimethylaminoethyl)-4-hydroxybenzylamine were identified as new urinary metabolites of pyrilamine by GC/MS. Thus, in addition to N- and O-demethylation, hydroxylation, and glucuronidation, N-debenzylation, N-depyridination and N-dedimethylaminoethylation were shown to be novel pathways for metabolism of tripelennamine and pyrilamine. The mechanism for N-depyridination and N-dealkylation is discussed.

The increasing incidence of cesarean birth has become quite controversial. The practice of delivering virtually all women with a prior cesarean section by repeat cesarean section is open to debate. In a large institutional practice, with rapid availability of all support services, selective attempts to deliver women vaginally, after a prior cesarean section, is appealing. A prospective 1-year study on all patients with a prior cesarean delivery commenced July 1, 1982. There were 1209 patients, of whom 751 (62%) underwent a trial of labor and 614 (82%) achieved vaginal delivery. There was no maternal mortality or perinatal mortality attributed to the trial of labor process. Oxytocin usage occurred in 38% of this population. The incidence of uterine rupture and scar dehiscence was similar in the various study subgroups. The overall group of women undergoing a trial of labor had significantly fewer postpartum complications and shorter hospital stays.

A retrospective analysis of 239 postdate patients who delivered within seven days of their last nonstress test between 1 July 1980 and 30 June 1981 was done to determine whether or not there was a relationship between variable fetal heart rate (FHR) decelerations, a decline in the FHR of at least 15 beats per minute and lasting 15 seconds, on the nonstress test and pregnancy outcome. Of the 505 nonstress tests, the results were considered either reactive (424 to 84%) or nonreactive (81 to 16%). Variable FHR decelerations or bradycardias were encountered on 95 nonstress tests (18.8%) in 80 (33.5%) postdate patients. Fetal heart rate bradycardia was encountered in nine patients (3.8%). Based on the last nonstress test, pregnancy outcome for the nonreactive group was less favorable than for the reactive group. However, when the reactive group was separated as to whether FHR decelerations or bradycardias were present or absent on the last test, the reactive group with FHR decelerations had a significant increase in meconium passage, cesarean delivery for fetal distress, and Apgar scores less than 7 at one minute. This group also had a similarly poor outcome as the nonreactive group of postdates patients. These data suggest that the nonstress test, when reactive without evidence of FHR decelerations, is a reliable indicator of fetal well-being in the postdate pregnancy. However, a reactive nonstress test with evidence of FHR decelerations is associated with a significant increase in perinatal morbidity.

The antepartum fetal surveillance (biochemical and biophysical) data of 140 pregnant diabetic patients were evaluated. We determined how often intervention occurred on the basis of abnormal tests and correlated each test with neonatal outcome. Fifteen of the total 140 patients had their pregnancies terminated because of abnormal biochemical and/or biophysical tests. An abnormal estriol (E3) value preceded the abnormal antepartum fetal heart rate testing in eight of 10 instances. We conclude that the major benefit of the antepartum fetal surveillance techniques, in this group of patients and under the present scheme, is in determining when not to intervene, thus allowing safe prolongation of pregnancy.

Meperidine esterase of the rat was studied. The enzyme activity was found in the liver microsomes but not in brain tissue or blood. The enzyme had an optimal activity between pH 8.0 to 9.5 and a temperature of 53 degrees-55 degrees C. The heat of activation was found to be 4.6 X 10(6) cal/mol and the KM 1.2 X 10(-4) M. The esterase activity of older male rats (200-350 g) was significantly higher than that of the younger group (150-175 g). There was no significant difference in specific activity of hepatic meperidine esterase between male and female rats, and between rats fasted for 20 hr and phenobarbital- and benzopyrene-treated rats and their respective control groups. However, the liver weight and the microsomal protein yield per g of liver of fasted rats were significantly smaller, and those of phenobarbital- and benzopyrene-treated rats were significantly larger, than those of the control group. The overall enzyme activity per liver of phenobarbital- and of benzopyrene-treated rats was therefore significantly increased. The specific enzyme activities in microsomes prepared by ultracentrifugation and by calcium aggregation were not significantly different, although the ultracentrifugation method resulted in a higher yield of hepatic microsomal protein. The enzyme activities in microsomes prepared by ultracentrifugation/or calcium aggregation and frozen at -20 degrees C up to 22 days were not significantly different from those of freshly prepared microsomes. The enzymatic activity was inhibited by cocaine hydrochloride, isocarboxazid, neostigmine methyl sulfate, alpha-naphthyl acetate, p-nitrophenyl acetate, paraoxon, propoxyphene hydrochloride, phenelzine sulfate, physostigmine sulfate, SKF 525-A, tranylcypromine sulfate, fluoride ions, methanol, and ethanol.

The role of twice-weekly plasma unconjugated estriol determinations in the prediction of fetal dysmaturity was studied in 663 patients seen at the Postdates Clinic of the Los Angeles County/University of Southern California Medical Center. The correlation between estriol and gestational age was - 0.055. According to the criteria of the Postdates Clinic protocol, sensitivity, specificity, predictive values of positive results, and those of negative results of estriol determinations in predicting fetal dysmaturity were 44.4, 80.6, 32.9, and 87.1%, respectively. The major deficiency of this test for the detection of fetal dysmaturity was in the less-than-ideal predictive value of a negative result: 13% of patients who had normal estriol values had dysmature infants. When estriol was less than 12 ng/ml and the value fell more than 20% from the previous level, the predictive value of fetal dysmaturity was 56%. In these circumstances, the termination of pregnancy is a reasonable consideration. Until a more sensitive test for fetal dysmaturity is developed, plasma unconjugated estriol determination will retain its role as a screening test in managing postterm pregnancies in a large obstetric population.

New morphine metabolites in the urine of guinea pigs, rats, rabbits, cats, monkeys, and humans were isolated with column chromatography, solvent extraction, and TLC and identified with TLC, GLC, and GLC-mass spectrometry. In addition to the known morphine metabolites, morphine N-oxide was isolated from the urine of guinea pigs, and alpha- and beta-dihydromorphines were isolated or detected in the urine of guinea pigs, rats, and rabbits. Monohydroxymorphine was identified tentatively in the urine of guinea pigs, rats, rabbits, and cats. Dihydroxymorphine was identified tentatively in the urine of guinea pigs, rats, and possibly, rabbits. Finally, beta- or gamma-isomorphine was identified tentatively in the urine of guinea pigs. The newly described morphine metabolites may be involved in some long lasting pharmacological effects of morphine.

Liver 9000 x g supernatant of rats from 1 day of age to adult was used as the enzyme source to study glucuronidation of morphine, O-demethylation of norcodeine and N-demtheylation and ester hydrolysis of meperidine. Uridine diphosphate glucuronyl transferase activity in 1-day-old rats was about one-fifth of that of the adult, increased to the adult level between 3 and 7 days of age and exceeded that of the adult when the rats were 28 days old. The activities of O- and N-demethylase were first observed in the liver of 3- and 7-day-old rats, respectively, and increased to the adult level at 35 days of age. Esterase activity was first observed in 14-day-old rats and increased rapidly to the adult level at 35 days of age. Drug metabolizing capacity for newborn rats, in terms of percentage of that of adults (calculated based on the specific enzyme activity, protein content of the liver and liver weight), was quite low for the first 2 weeks of life, ranging from undetectable to less than 5% of the adult level. The capacity increased during the next 3 weeks, reaching about 50 to 75% of adult activities by the 35th day.

The fetal startle reflex was studied in an attempt to provide an objective and quantitative estimate of the fetal neurological condition. This reflex is a normal response to a combined sound-vibratory stimulus in the healthy infant born after 30 weeks of gestation. It consists of a generalized paroxysmal motion that involves the whole body. Thirty women with uncomplicated pregnancies, who subsequently delivered healthy infants, were studied at term. Fetal movements were monitored by means of a real-time scanner. Placement of the transducer was such that it allowed for visualization of the long axis of the fetal forearm. A 3-second stimulus was delivered on the maternal abdomen over the fetal head with use of an artificial larynx. This device generates a mixed sound-vibratory output of 100 dB and 85 Hz. Sufficient visualization of the plane of forearm motion was possible 68% of the time, thus allowing for measurement of the duration of this motion. The results indicate that the mean duration of forearm motion in response to a 3-second sound-vibratory stimulus is 8.2 +/- 2.3 seconds (+/- SEM). Since an immediate forearm motion was detected each time that a stimulus was applied, we conclude that the startle reflex does indeed exist in the fetus. This simple means of assessing the neurological state of the fetus may provide a way to evaluate fetal tone as it applies to antenatal fetal assessment.

A new, practical approach to perinatal data processing for a large obstetric population is described. This was done with a microcomputer for data entry and a mainframe computer for data reduction. The Screen Oriented Data Access (SODA) program was used to generate the data entry form and to input data into the Apple II Plus computer. Data were stored on diskettes and transmitted through a modern and telephone line to the IBM 370/168 computer. The Statistical Analysis System (SAS) program was used for statistical analyses and report generations. This approach was found to be most practical, flexible, and economical.

With the techniques of column chromatography, TLC, and GLC, morphine, 6-acetylmorphine, normorphine, morphine 3-glucuronide, 6-acetylmorphine 3-glucuronide, and normorphine glucuronide were identified as metabolites of diacetylmorphine (heroin) in the urine of humans administered 10 mg iv/70 kg body weight.

This study investigates a number of parameters that influence the neurotoxic effects of 3,4-methylenedioxymethamphetamine (MDMA) on serotonin (5-HT) neurons in brain. Both the dose and number of injections of MDMA affect the degree of neurotoxicity on 5-HT axons and terminals as assessed by decreases in the content of 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) and the density of 5-HT uptake sites. Repeated systemic administration of various doses of MDMA (5-20 mg/kg twice daily for 4 consecutive days) results in dose-dependent decreases in 5-HT, 5-HIAA and 5-HT uptake sites. Increasing the number of injections of MDMA resulted in progressively greater reductions in 5-HT and 5-HIAA which occurred prior to decreases in 5-HT uptake sites. In contrast, no significant changes were observed in the density of norepinephrine uptake sites following single or repeated injections of 20 mg/kg MDMA. With respect to neuronal regeneration, following an initial 90% loss of 5-HT uptake sites after treatment with MDMA, the recovery of these sites occurred over a protracted period of time; a marked 25% reduction was seen at 6 months and the concentration of 5-HT uptake sites returned to control levels at 12 months following treatment with MDMA. Pretreatment with the selective 5-HT uptake blocker, citalopram, prior to each injection of MDMA prevented the neurotoxic effects of MDMA on the 5-HT parameters described above suggesting that active uptake of MDMA or a MDMA-related substance into brain 5-HT neurons was involved in the neurotoxic actions of the drug. In addition, the neurodegenerative effects of MDMA on 5-HT neurons exhibited some species specificity as comparable decreases in cerebral cortical 5-HT, 5-HIAA and 5-HT uptake sites were observed in rat and guinea pig while no significant changes in any of these serotonergic parameters were seen in mouse brain.

From 1978 to 1982, 70 cases of emergency hysterectomy for obstetric hemorrhage were performed at Los Angeles County/University of Southern California Women's Hospital. Sixty hysterectomies followed cesarean section, and ten were performed for hemorrhage after vaginal delivery. The most common indication for hysterectomy was atony (43%) followed by placenta accreta (30%), uterine rupture (13%), extension of a low transverse incision (10%), and leiomyomata preventing uterine closure and hemostasis (4%). Hysterectomies performed for atony had a significant association with the following factors when compared to hysterectomies performed for other indications: 1) amnionitis, 2) cesarean section for labor arrest, 3) oxytocin augmentation of labor, 4) MgSO4 infusion, and 5) fetal weight. Fifty-seven percent of hysterectomies performed for placenta accreta were associated with a previous cesarean section. During the study period, 53% of all patients presenting at term with both a placenta previa and one or more previous cesarean sections, subsequently underwent hysterectomy for placenta accreta. Even with a broad inclusion of risk factors, only 74% of patients developing a hemorrhagic complication leading to hysterectomy can be identified before delivery.

Procedures were developed for TLC identification and GLC determination of meperidine and its metabolites, i.e., p-hydroxymeperidine, normeperidine, and meperidinic and normeperidinic acids. Meperidine, p-hydroxymeperidine, and normeperidine were extracted with ether from biological fluids at pH 10, whereas meperidinic and normeperidinic acids and conjugated metabolites remained in the aqueous phase. The residue, upon evaporation of the extract to dryness, was derivatized with trifluoroacetic anhydride and gas chromatographed. Total (free and conjugated) meperidinic and normeperidinic acids in the aqueous phase were converted and determined as meperidine and normeperidine, respectively. A preliminary result of urinary disposition of meperidine and its metabolites in the rat is presented. The identity of these metabolites was confirmed with GLC-mass spectrometry.

The urine of male and female mice, rats, guinea pigs, rabbits, cats, and dogs, given meperidine hydrochloride, 20--40 mg/kg ip, was analyzed by GLC for meperidine, normeperidine, p-hydroxymeperidine, and total (free and conjugated) meperidinic and normeperidinic acids. More than 90% of the excreted drugs was found in the 24-hr urine. Meperidine was observed in the urine of mice, rats, guinea pigs, and cats, but only a trace amount was observed in the urine of rabbits and dogs. Normeperidine, p-hydroxymeperidine (except in the mice), and total meperidinic and normeperidinic acids were observed in all species. All of the species studied have the capacity to N-demethylate meperidine to normeperidine and to hydrolyze meperidine and normeperidine to their respective acids. The male has a higher N-demethylating activity that the female with the exception of mice. Ester hydrolysis is a major metabolic pathway for meperidine metabolism.

This study explores the relationship between fetal heart rate variability and fetal breathing movements in the term fetus. Fourier analysis was applied to fetal heart rate variability during fetal breathing and nonbreathing episodes. A distinct component in the order of 0.7 to 0.95 Hz was demonstrated in fetal heart rate variability during breathing episodes. These frequencies have the same distribution as the corresponding rate of breathing and therefore indicate that respiratory sinus arrhythmia exists in the term fetus.