Biomedical subjects

C Chen

Publications and source records attributed to C Chen.

At least 361 records · Page 20Linked to original sources

PubMed2000

Peroxisome proliferator-activated receptor alpha-null mice lack resistance to acetaminophen hepatotoxicity following clofibrate exposure.

The purpose of this study was to investigate whether activation of the nuclear receptor PPARalpha is needed for protection from acetaminophen (APAP) hepatotoxicity produced by repeated administration of the peroxisome proliferator clofibrate (CFB). Female wild-type and PPARalpha-null mice received corn oil vehicle or 500 mg CFB/kg, ip, daily for 10 days. They were then fasted overnight (18 h) and either killed at 4 or 24 h after challenge with 400 mg APAP/kg. Controls received 50% propylene glycol vehicle only. In this model of CFB hepatoprotection, liver injury was assessed by measuring plasma sorbitol dehydrogenase activity and by histopathology at 24 h after APAP challenge. Significant hepatocellular necrosis was evident in both corn oil-pretreated PPARalpha-null and wild-type mice at 24 h after APAP challenge. In agreement with previous studies, CFB-pretreated wild-type mice showed marked protection against APAP toxicity. In contrast, CFB did not provide protection against APAP hepatotoxicity in the PPARalpha-null mice. Similarly, at 4 h after APAP challenge, hepatic glutathione depletion and selective arylation of cytosolic proteins were reduced significantly in CFB-pretreated wild-type mice, but not in PPARalpha-null mice. The lack of changes in APAP binding and NPSH depletion in CFB-pretreated, PPARalpha-null mice is consistent with the presence of significant liver injury at 24 h in this treatment group. These findings demonstrate that the protection against APAP hepatotoxicity by peroxisome proliferator treatment is mediated by the activation of PPARalpha.

Acetaminophen↗

PubMed2000

Expression of hepatocyte growth factor and its receptor c-met in the ovine uterus.

Epithelial-mesenchymal interactions (EMI) are necessary for epithelial cell proliferation, differentiation, and function in the uterus and are mediated, in part, by paracrine growth factors of stromal origin. The objective of this study was to determine if hepatocyte growth factor (HGF, scatter factor) and its receptor c-met were present in the ovine uterus and to characterize their temporal and spatial expression during the estrous cycle and pregnancy. Reverse transcription-polymerase chain reaction was used to clone partial cDNAs for ovine HGF and c-met from endometrial total RNA. Northern blot analysis of endometrial RNA revealed expression of a 6-kb mRNA for HGF and an 8-kb mRNA for c-met in ovine endometrium. In situ hybridization demonstrated that HGF mRNA was expressed by stromal cells of the endometrium, whereas c-met mRNA was localized exclusively to luminal and glandular epithelial cells. In the early conceptus, HGF mRNA was expressed by chorioallantoic mesenchyme, and c-met was expressed by trophectoderm. Steady-state levels of endometrial c-met mRNA increased after Day 9 in both cyclic and pregnant ewes. The HGF mRNA was expressed during both the estrous cycle and early pregnancy. Results indicate that HGF is a stromal-derived paracrine growth factor in the ovine uterus and placenta that is potentially involved in endometrial epithelial-stromal interactions and chorioallantoic stromal-trophectodermal interactions. In the ovine uterus, HGF may stimulate epithelial morphogenesis and differentiated function required for establishment and maintenance of pregnancy, conceptus implantation, and placentation.

Animals↗

PubMed2000

Fibroblast growth factor-10: a stromal mediator of epithelial function in the ovine uterus.

Fibroblast growth factor-10 (FGF-10) is a stromal-derived paracrine growth factor considered to be important during embryogenesis; however, its expression by cells in the female reproductive tract has not been investigated. Therefore, an ovine FGF-10 cDNA was cloned from an ovine endometrial cDNA library to investigate expression and potential paracrine characteristics of FGF-10 in the ovine uterus. The ovine FGF-10 cDNA encodes a protein of 213 amino acids and possesses an unusually long 5' untranslated region (UTR). In situ hybridization demonstrated that ovine FGF-10 mRNA was expressed by endometrial stromal cells and by mesenchymal cells of the chorioallantoic placenta. The mRNA for FGF-7, a homologue of FGF-10, was localized in the tunica muscularis of blood vessels in endometrium and myometrium. In contrast, FGF receptor 2IIIb, the high-affinity receptor for both FGF-10 and FGF-7, was expressed exclusively in luminal epithelium, glandular epithelium, and placental trophectoderm. The in vivo spatial expression pattern suggests that FGF-10 is a novel endometrial stromal cell-derived mediator of uterine epithelial and conceptus trophectodermal functions. The nonoverlapping spatial patterns of expression for FGF-10 and FGF-7 in ovine uterus and conceptus suggest independent roles in uterine function and conceptus development.

Amino Acid Sequence↗

PubMed2000

Cold-fluid equilibrium for a corkscrewing elliptic beam in a variably focusing channel

It is shown that there exists a new class of cold-fluid corkscrewing elliptic beam equilibria for ultrahigh-brightness, space-charge-dominated beam propagation through a linear focusing channel consisting of uniform solenoidal, periodic solenoidal, and/or alternating-gradient quadrupole focusing magnets in an arbitrary arrangement including field tapering. The equilibrium beam density and flow velocity profiles and equilibrium self-electric and self-magnetic fields are determined by solving generalized beam envelope equations. In proper limits, such cold-fluid corkscrewing elliptic beam equilibria recover many familiar beam equilibria in beam physics, including the round rigid-rotor Vlasov beam equilibria in uniform and periodic solenoidal focusing fields and the Kapchinskij-Vladimirskij beam equilibrium in an alternating-gradient quadrupole focusing field. For beams with negligibly small emittance, the equilibrium solutions are validated with self-consistent simulations. Examples and applications of the present equilibrium beam theory are discussed. As an important application of the present equilibrium beam theory, a general technique is developed and demonstrated with an example to control large-amplitude density and flow velocity fluctuations (such as beam hollowing and halo formation) often observed in ultrahigh-brightness beams.

Journal Article↗

PubMed2000

Cell-specific and conditional expression of caffeoyl-coenzyme A-3-O-methyltransferase in poplar.

Caffeoyl coenzyme A-3-O-methyltransferase (CCoAOMT) plays an important role in lignin biosynthesis and is encoded by two genes in poplar (Populus trichocarpa). Here, we describe the expression pattern conferred by the two CCoAOMT promoters when fused to the gus-coding sequence in transgenic poplar (Populus tremula x Populus alba). Both genes were expressed similarly in xylem and differentially in phloem. In xylem, expression was preferentially observed in vessels and contact rays, whereas expression was barely detectable in storage rays and fibers, suggesting different routes to monolignol biosynthesis in the different xylem types. Furthermore, after wounding, fungal infection, and bending, the expression of both genes was induced concomitantly with de novo lignin deposition. Importantly, upon bending and leaning of the stem, the cell-specific expression pattern was lost, and both genes were expressed in all cell types of the xylem. CCoAOMT promoter activity correlated well with the presence of the CCoAOMT protein, as shown by immunolocalization. These expression data may explain, at least in part, the heterogeneity in lignin composition that is observed between cell types and upon different environmental conditions.

Blotting, Western↗

PubMed2000

A double-blind, placebo-controlled study of topiramate in adult patients with refractory partial epilepsy.

PURPOSE: The efficacy and safety of topiramate (TPM) as adjunctive therapy in the treatment of adult Chinese patients with refractory partial epilepsy were investigated in a randomized, double-blind, placebo-controlled study. METHODS: A total of 46 patients who had four or more complex partial seizures with or without secondary generalization within an 8-week baseline phase were enrolled. Patients were assigned randomly to receive TPM (n = 23) or placebo (n = 23). TPM or placebo was titrated to target doses of 300 mg/d for 6 weeks and maintained at stabilized levels for another 8 weeks. Concomitant antiepileptic drugs remained at constant previous levels during the trial. RESULTS: In all, 41 patients completed the trial (TPM group, n = 20; placebo group, n = 21). The proportion of patients with a > or =50% reduction from baseline in complex partial seizures was 11 of 23 (47.8%) in the TPM group and 3 of 23 (13.0%) in the placebo group (p = 0.01). In addition, patients treated with TPM had significantly better investigator (p = 0.014) and patient (p = 0.0005) global assessment scores than patients in the placebo group. Adverse events were mostly mild and transient, with no significant differences between treatment groups. Two patients with TPM therapy complained of weight loss. Routine blood cell counts and other laboratory results showed no significant changes from baseline in either treatment group. CONCLUSIONS: TPM 300 mg/d is effective and well tolerated as treatment for refractory partial epilepsy in adults.

Adolescent↗

PubMed2000

Altered antigenicity is seen in the lipopolysaccharide profile of non-serotypeable Actinobacillus actinomycetemcomitans strains.

Non-serotypeable Actinobacillus actinomycetemcomitans strains may be derived from the serotypeable ones. In the present study, we compared the outer membrane proteins (OMPs) and lipopolysaccharides (LPSs) of serotypeable and non-serotypeable A. actinomycetemcomitans strains (n=24) of the same genotype in the same subject (n=6) to find out if alterations on the cell-surface contribute to the non-serotypeability. Serotypeable and non-serotypeable A. actinomycetemcomitans strains showed great similarity in the OMP patterns both within and between subjects. Using serotype-specific antisera, clear immunoblotting LPS profiles in the O-antigenic region were seen in serotype b and c strains but not in non-serotypeable strains from the same subjects. The results suggest that changes in LPS lead to the altered antigenicity of non-serotypeable A. actinomycetemcomitans strains.

Actinobacillus Infections↗

PubMed2000

Molecular identification of Dialister pneumosintes in subgingival plaque of humans.

Dialister pneumosintes is a nonfermentative, anaerobic, gram-negative rod that grows with small, circular, transparent, shiny, smooth colonies on blood agar. Even though D. pneumosintes has been recovered from deep periodontal pockets, little is known about the relationship between the organism and destructive periodontal disease. This study describes a rapid PCR method to identify D. pneumosintes in periodontal samples. The PCR identification method detected as little as 10 pg of D. pneumosintes DNA or about 1 to 10 cells without nonspecific amplification of various periodontopathic bacteria. Twelve of 22 subgingival samples from adult periodontitis lesions yielded D. pneumosintes either by culture or by PCR identification. In culture-positive samples, D. pneumosintes averaged 3.9% (0.001 to 10.8%) of total isolates. Studies are needed to delineate virulence factors of D. pneumosintes pertinent to periodontal disease.

Cloning, Molecular↗

PubMed2000

The Rel/NF-kappaB family directly activates expression of the apoptosis inhibitor Bcl-x(L).

The transcription factors of the Rel/NF-kappaB family are key regulators of immune and inflammatory responses and contribute to lymphocyte proliferation, survival, and oncogenesis. The absolute correlation between the antiapoptotic and oncogenic activities of the Rel/NF-kappaB oncoprotein v-Rel emphasizes the importance of characterizing the death antagonists under NF-kappaB control. Our recent finding that the prosurvival Bcl-2 homolog Bfl-1 (also called A1) is a direct transcriptional target of NF-kappaB raised the issue of whether NF-kappaB is a specific or global regulator of death antagonists in the Bcl-2 family. Here, we demonstrate that NF-kappaB differentially regulates the expression of particular Bcl-2-related death inhibitors and that it directly activates the expression of Bcl-x(L). While Bcl-x(L) was significantly upregulated by c-Rel and RelA, Bcl-2 was not. Importantly, stimuli that activate endogenous NF-kappaB factors also upregulated bcl-x gene expression and this effect was antagonized by an inhibitor of NF-kappaB activity. The expression of bcl-x suppressed apoptosis in the presence or absence of NF-kappaB activity. Functional analysis of the bcl-x promoter demonstrated that it is directly controlled by c-Rel. These results establish that NF-kappaB directly regulates the expression of distinct prosurvival factors in the Bcl-2 family, such as Bcl-x(L) and Bfl-1/A1. These findings raise the possibility that some of these factors may contribute to oncogenesis associated with aberrant Rel/NF-kappaB activity.

Apoptosis↗

PubMed2000

Exposure to benzene, occupational stress, and reduced birth weight.

OBJECTIVES: The association between birth weight and exposure to benzene, work stress, and other occupational and environmental hazards was investigated. METHODS: In a large petrochemical industry, 792 pregnant workers were enrolled and followed up through delivery between May 1996 and December 1998. Exposure to benzene and other solvents was assessed by an industrial hygienist based on each woman's job title and workplace information. Other occupational and environmental exposures and personal information, including perceived work stress, exposure to noise, physical exertion at work, and passive smoking, were obtained by an interview questionnaire. Univariate and multivariate regression models were used to examine the individual and combined associations of occupational and environmental exposures with birth weight, with adjustment for major confounders including gestational age. RESULTS: In the univariate model, birth weight was negatively associated with exposure to benzene (-58 g (95% confidence interval (95% CI), -115 to -2)) and with work stress (-84 g (95% CI, -158 to -10)). In the multivariate model, there was a significant interaction between exposure to benzene and work stress relative to reduced birth weight, after adjustment for other environmental and occupational exposures and personal variables. Adjusted mean birth weight was 3445 g (95% CI 3401 to 3489) among those with neither exposure, 3430 g for those with exposure to benzene only, 3426 g for those with work stress only, and 3262 g (95% CI 3156 to 3369) for those with both exposures. In other words, there was 183 g (95% CI 65 to 301) reduction in birth weight among those with both exposure to benzene and work stress compared with those with neither exposure. Other work or environmental factors could not explain these findings. CONCLUSIONS: Low level exposure to benzene and work stress interact to reduce birth weight in this population.

Adult↗

PubMed2000

Functional expression of three P2X(2) receptor splice variants from guinea pig cochlea.

ATP has been suggested to act as a neurotransmitter or a neuromodulator in the cochlea. The responses to ATP in different cell types of the cochlea vary in terms of the rate of desensitization and magnitude, suggesting that there may be different subtypes of P2X receptors distributed in the cochlea. Recently three ionotropic P2X(2) receptor splice variants, P2X(2-1), P2X(2-2), and P2X(2-3,) were isolated and sequenced from a guinea pig cochlear cDNA library. To test the hypothesis that these different splice variants could be expressed as functional homomeric receptors, the three P2X(2) receptor variants were individually and transiently expressed in human embryonic kidney cells (HEK293). The biophysical and pharmacological properties of these receptors were characterized using the whole cell patch-clamp technique. Extracellular application of ATP induced an inward current in HEK293 cells containing each of the three splice variants in a dose-dependent manner indicating the expression of homomeric receptors. Current-voltage (I-V) relationships for the ATP-gated current show that the three subtypes of the P2X(2) receptor had a similar reversal potential and an inward rectification index (I(50 mV)/I(-50 mV)). However, the ATP-induced currents in cells expressing P2X(2-1) and P2X(2-2) variants were large and desensitized rapidly whereas the current in those cells expressing the P2X(2-3) variant was much smaller and desensitized slower. The order of potency to ATP agonists was 2-MeSATP > ATP > alpha,beta -MeATP for all three expressed splice variants. The ATP receptor antagonists suramin and PPADS reduced the effects of ATP on all three variants. Results demonstrate that three P2X(2) splice variants from guinea pig cochlea, P2X(2-1), P2X(2-2), and P2X(2-3), can individually form nonselective cation receptor channels when these subunits are expressed in HEK293 cells. The distinct properties of these P2X(2) receptor splice variants may contribute to the differences in the response to ATP observed in native cochlear cells.

Adenosine Triphosphate↗

PubMed2000

Familial aggregation of bronchodilator response: a community-based study.

We investigated familial aggregation of bronchodilator response (BDR) among 4,946 subjects selected from 1,161 index families with asthma in a rural community in China. Each family unit consisted of both parents and their first and subsequent offspring, aged 8-20. Raw BDR measurements, defined as the percentage change in FEV(1) after 180 microg of albuterol, were adjusted to account for sex, age, height, weight, education, smoking, asthma, wheeze, and allergy status. Using these adjusted BDR values, we found significant correlation for father-first offspring pairs, mother-first offspring pairs, mother-subsequent offspring pairs, and first offspring-subsequent offspring pairs. The overall magnitude of the correlation coefficient (0.088-0.165) suggests a modest degree of familial clustering. The largest odds ratio was seen for subsequent offspring who had mothers and first offspring with adjusted BDR values above the median: 3.10 (95% CI: 1.85-5.20) in these index families with asthma. Thus, our data support a significant familial aggregation of BDR in this Chinese population, which points to a role of genetic factors in BDR.

Administration, Inhalation↗

PubMed2000

Psychiatric morbidity and illness experience of primary care patients with chronic fatigue in Hong Kong.

OBJECTIVE: The authors' goal was to examine the prevalence and experience of psychiatric morbidity among primary care patients with chronic fatigue in Hong Kong. METHOD: One hundred adult patients with medically unexplained fatigue for 6 or more months were assessed with the Explanatory Model Interview Catalogue, psychopathological rating scales, and an enhanced version of the Structured Clinical Interview for DSM-III-R. RESULTS: The lifetime prevalence of DSM-III-R depressive and anxiety disorders was 54%. Current depressive and anxiety disorders were identified in 28 patients, who exhibited more psychopathology and functional impairment than other patients. Thirty-three patients had somatoform pain disorder, and 30 had undifferentiated somatoform disorder, but most of them could also be diagnosed as having shenjing shuairuo (weakness of nerves) and, to a lesser extent, ICD-10 neurasthenia. Chronic fatigue syndrome diagnosed according to the 1988 Centers for Disease Control criteria was rare (3%) and atypical. Generally, patients mentioned fatigue if asked, but pains (36%), insomnia (20%), and worries (13%) were the most troublesome symptoms. Most patients attributed illness onset to psychosocial sources. CONCLUSIONS: Psychiatric morbidity was common among primary care patients with chronic fatigue. Subthreshold psychiatric morbidity was very common and was more validly represented by the disease construct of shenjing shuairuo or neurasthenia than somatoform disorder.

Adolescent↗

PubMed2000

A porcine model of carotid artery thrombosis for thrombolytic therapy and angioplasty: application of PTFE graft-induced stenosis.

PURPOSE: To develop a porcine carotid artery thrombosis model for the evaluation of thrombolytic therapy and adjunctive angioplasty procedures. METHODS: Bilateral carotid thrombosis was induced in 16 pigs using endothelial crush injury followed by external polytetrafluoroethylene (PTFE, 5 x 2 cm2) wrap placement to create segmental carotid stenosis. Light microscopy was used to examine thrombus composition. Selective carotid catheterization was performed via a femoral approach. Two hours following carotid artery occlusion, a urokinase (250,000 IU) and heparin (1000 U) solution was pulse-sprayed in 1 carotid artery while the contralateral vessel received the control saline vehicle. The efficacy of thrombolytic therapy was assessed using carotid arteriography and intravascular ultrasound. The feasibility and technical efficacy of balloon angioplasty within the carotid stenosis model were also evaluated. RESULTS: Carotid artery occlusion occurred in 30 +/- 6 minutes following endothelial injury plus PTFE wrap placement. Histological examination of carotid arteries showed endothelial irregularity with fibrin-rich and platelet-rich thrombus. Urokinase was effective in recanalizing all occluded arteries (100%), while the control saline vehicle showed no effective thrombolysis (p < 0.001). Angioplasty was successful in restoring normal diameter in all arteries (100%). CONCLUSIONS: This carotid artery thrombosis model, which incorporates intimal injury with segmental stenosis, is simple to create and reproducible. It provides not only a model for the evaluation of thrombolytic therapy but also a practical training tool for adjunctive endovascular interventions.

Angiography↗

PubMed2000

An endovascular model of carotid stenosis for the evaluation of thrombolysis and angioplasty.

PURPOSE: To develop a porcine carotid artery thrombosis model using a novel stent-graft device to evaluate the efficacy of thrombolytic therapy and angioplasty procedures. METHODS: An endovascular device made from a tapered polytetrafluoroethylene graft inverted in a self-expanding nitinol stent was delivered to bilateral carotid arteries via a right femoral approach in 16 pigs. Carotid thrombotic occlusion ensued from flow stasis created by the intrastent stenosis. Via selective carotid catheterization from a femoral approach, urokinase (250,000 IU) was pulse-sprayed in one carotid artery while a control saline solution was infused in the contralateral vessel; delivery times were 1 hour, 8 hours, 3 days, or 6 days after carotid occlusion (4 animals per time period). After thrombolysis, balloon angioplasty was performed to maintain carotid patency. Arteriography and intravascular ultrasound were used to evaluate the efficacy of thrombolysis. Light microscopy was used for histological analysis of the thrombus. RESULTS: Carotid artery occlusion occurred in 15+/-8 minutes after stent-graft placement in all animals. Urokinase was effective in recanalizing all occluded arteries in the 1-hour, 4-hour, and 3-day groups (100%) but was effective in only 2 of 4 animals in the 6-day group (p < 0.05). Overall thrombolytic efficacy was 78%+/-7%. Control saline solution showed no thrombolytic effect (p < 0.001). Angioplasty successfully restored normal luminal diameter in all fully lysed arteries (100%). Histological analysis showed fibrin-predominant thrombus with a varying degree of platelet deposition. CONCLUSIONS: This endovascular approach, which creates a carotid stenosis using this novel stent-graft device, is reliable in producing carotid thrombosis. In our model, thrombolytic therapy was effective in restoring luminal patency, and the intraluminal stenosis is amenable to balloon angioplasty. The model is useful for the evaluation of antithrombotic therapy and adjunctive endovascular interventions.

Angioplasty, Balloon↗

PubMed2000

Progress towards the development of non-peptide orally-active gonadotropin-releasing hormone (GnRH) antagonists: therapeutic implications.

Gonadotropin-releasing hormone (GnRH) is a decapeptide (pGlu-His-Trp-Ser-Tyr-Gly-Leu-Arg-Pro-Gly.NH2) which is produced from a precursor polypeptide in hypothalamic neurons and secreted in a pulsatile fashion to stimulate the secretion of LH and FSH via its interaction with a cognate receptor on gonadotropes. Low doses of the native peptide delivered in a pulsatile manner to mimic that found in the hypothalamic portal vessels restore fertility in hypogonadal patients, and are also effective in treating cryptorchidism and delayed puberty. Administration of high doses of GnRH, or agonist analogues, causes desensitization of the gonadotrope with consequent decline in gonadal gametogenesis and steroid and peptide hormone synthesis. This phenomenon finds extensive therapeutic application in clinical medicine in a wide spectrum of disease (Table 1). In addition, GnRH analogues have promise as new generation male and female contraceptives in conjunction with steroid hormone replacement. GnRH antagonists inhibit the reproductive system through competition with endogenous GnRH for the receptor and, in view of their rapid effects, are being increasingly used for the above mentioned applications. The peptide agonists and antagonists currently available require parenteral administration, typically in the form of long-acting depots. A new generation of non-peptide GnRH antagonists are beginning to emerge which should allow oral administration and, therefore, may provide greater flexibility of dosing, lower costs and increased patient acceptance.

Administration, Oral↗

PubMed2000

Prospective study of exposure to environmental tobacco smoke and dysmenorrhea.

Dysmenorrhea is a common gynecologic disorder in women of reproductive age. Previous studies have found an association between current cigarette smoking and prevalence of dysmenorrhea. This study investigated the association between exposure to environmental tobacco smoke (ETS) and the occurrence of dysmenorrhea among women without a history of this disorder. The study population consisted of 165 newly wed, nonsmoking Chinese women (in Shenyang, China), who intended to get pregnant and who had no past history of dysmenorrhea at the time of enrollment. These women completed a baseline questionnaire interview upon enrollment and were prospectively followed by daily diary. Dysmenorrhea was defined as a diary recording of abdominal pain or low back pain for at least 2 days during a menstrual period. A subject's ETS exposure was defined as the mean number of cigarettes smoked per day at home by household members over an entire menstrual cycle before the menstrual period. A logistic regression model was used to assess the effect of ETS on the risk of dysmenorrhea, with adjustment for age, body mass index, education, season, area of residence, occupation, shift work, perceived stress, passive smoking at work, and occupational exposure to chemical hazards, dust, and noise. Generalized estimating equations were used to account for autocorrelations as a result of multiple cycles per subject. This report is based on 625 prospectively followed menstrual cycles with complete baseline and diary data. ETS exposure was reported in 77% of cycles, within which average daily exposures throughout the cycle ranged from 0.02 to 10. 3 cigarettes. The incidence of dysmenorrhea was 9.7% and 13.3% among nonexposed and exposed cycles, respectively. Among ETS-exposed cycles, there was a positive dose-response relationship between the numbers of cigarettes smoked and the relative risk of dysmenorrhea. The adjusted odds ratios of dysmenorrhea associated with "low," "middle," and "high" tertiles of ETS exposure versus no exposure were 1.1 [95% confidence interval (CI), 0.5-2.6], 2.5 (CI, 0.9-6.7), and 3.1 (CI, 1.2-8.3), respectively. The findings were consistent with those of analyses limited to the first follow-up menstrual cycle from each woman. These data suggest a significant dose-response relationship between exposure to ETS and an increased incidence of dysmenorrhea in this cohort of young women.

Adult↗

PubMed2000

A multicenter drug use surveillance of intravenous immunoglobulin utilization in US academic health centers.

BACKGROUND: The role of intravenous immunoglobulin (IVIG) in treating a variety of diseases is controversial and under active investigation for at least two reasons: first, a severe shortage of IVIG products exists in the US; second, numerous off-label (not specified in the Food and Drug Administration [FDA]-approved label) uses for IVIG have been, and continue to be, described in the literature. However, most off-label uses are not supported by evidence from properly designed clinical trials. OBJECTIVE: To assess inpatient use of IVIG in a sample of US academic health centers and to compare it with published evidence-based model guidelines for IVIG use. METHODS: Data on the use of IVIG and subsequent clinical outcomes in 251 patients were collected prospectively from 12 institutions. Recommendations from consensus guidelines were used to categorize patients who received IVIG into one of four groups: labeled uses; off-label, recommended; off-label, recommended as alternative; and off-label, not recommended. Outcomes were scored according to guideline criteria. RESULTS: One hundred seven patients (43%) received IVIG for indications contained in the FDA-approved product label, 130 patients (52%) received IVIG for off-label indications, and 14 (5%) received undefined treatment. Among all patients administered IVIG, 31 (12%) were treated for off-label recommended reasons; 64 (26%) received off-label recommended as alternative therapy; and 35 (14%) received off-label not recommended therapy, as defined by model guidelines. Outcomes were not significantly different between the groups. CONCLUSIONS: Our findings suggest that IVIG continues to be used to treat a wide variety of conditions not specified in the product label. Furthermore, a substantial proportion of the reported off-label uses are not recommended according to evidence-based guidelines.

Academic Medical Centers↗