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PubMed1994

Cholestatic hepatitis after ingestion of chaparral leaf: confirmation by endoscopic retrograde cholangiopancreatography and liver biopsy.

The use of herbal and other "natural" health products by healthy and ill people is more common than is appreciated by many health care providers. Since most of these substances are not categorized as medicines, they are exempt from U.S. Government approval processes, and are essentially uncontrolled. In this article we describe a patient who developed painless jaundice, fatigue, and pruritus after taking chaparral tablets, 160 mg/day, for approximately 2 months. Serial liver biopsies and serum chemistries documented severe cholestasis and hepatocellular injury, i.e., a severe cholangiolitic hepatitis. Serum enzyme levels were markedly elevated: alk. phos. to four-fold, alanine aminotransferase and aspartate aminotransferase to 25-fold, total bilirubin to 30-fold, and gamma-glutamyl transpeptidase to 35-fold. Endoscopic retrograde cholangiopancreatography showed smooth, but severely narrowed biliary ducts without sclerosing cholangitis, distal obstruction, tumor, or stenosis. The diagnosis remained in doubt until the publication of two cases of chaparral hepatotoxicity. Because of the similarity of our patient's illness to those cases we concluded that chaparral was almost certainly the cause. Chaparral, also known as creosote or greasewood, is used by some practitioners to treat a diverse group of ailments including ethanol withdrawal. This report should heighten the awareness by primary care physicians and gastroenterologists that any chaparral herbal preparation is a potential hepatotoxin that can lead to serious illness.(ABSTRACT TRUNCATED AT 250 WORDS)

Alcoholism↗
PubMed2003

Gene expression profile of AIDS-related Kaposi's sarcoma.

BACKGROUND: Kaposi's Sarcoma (KS) is a proliferation of aberrant vascular structures lined by spindle cells, and is caused by a gammaherpes virus (HHV8/KSHV). Its course is aggravated by co-infection with HIV-1, where the timing of infection with HIV-1 and HHV8 is important for the clinical outcome. METHODS: In order to better understand the pathogenesis of KS, we have analysed tissue from two AIDS-KS lesions, and from normal skin by serial analysis of gene expression (SAGE). Semi-quantitative RT-PCR was then used to validate the results. RESULTS: The expression profile of AIDS-related KS (AIDS-KS) reflects an active process in the skin. Transcripts of HHV8 were found to be very low, and HIV-1 mRNA was not detected by SAGE, although it could be found using RT-PCR. Comparing the expression profile of AIDS-KS tissue with publicly available SAGE libraries suggested that AIDS-KS mRNA levels are most similar to those in an artificially mixed library of endothelial cells and leukocytes, in line with the description of KS lesions as containing spindle cells with endothelial characteristics, and an inflammatory infiltrate. At least 64 transcripts were found to be significantly elevated, and 28 were statistically downregulated in AIDS-KS compared to normal skin. Five of the upregulated mRNAs, including Tie 1 and sialoadhesin/CD169, were confirmed by semi-quantitative PCR to be elevated in additional AIDS-KS biopsies. Antibodies to sialoadhesin/CD169, a known marker of activated macrophages, were shown to specifically label tumour macrophages. CONCLUSION: The expression profile of AIDS-KS showed 64 genes to be significantly upregulated, and 28 genes downregulated, compared with normal skin. One of the genes with increased expression was sialoadhesin (CD169). Antibodies to sialoadhesin/CD169 specifically labelled tumour-associated macrophages, suggesting that macrophages present in AIDS-KS lesions belong to a subset of human CD169+ macrophages.

Acquired Immunodeficiency Syndrome↗
PubMed2026

Circulating Tumor DNA in Breast Cancer: A Liquid Biopsy Revolution for Non-Invasive Genomic Profiling and Clinical Decision-Making.

Breast cancer remains the most frequently diagnosed cancer and a leading cause of cancer-related mortality among women worldwide, underscoring the need for accurate, minimally invasive biomarkers to support precision oncology. Conventional tissue biopsy remains the standard for molecular characterization but is limited by its invasiveness, inability to capture spatial and temporal tumor heterogeneity, and challenges in serial monitoring. Circulating tumor DNA (ctDNA), a tumor-derived fraction of cell-free DNA, has emerged as a promising liquid biopsy biomarker capable of providing real-time genomic information throughout disease progression. This narrative review examines recent advances in ctDNA biology, analytical technologies, clinical applications, current limitations, and future directions in breast cancer management. A structured literature search of PubMed/MEDLINE, Scopus, Embase, Web of Science, and Google Scholar identified relevant English-language publications from 2015 to 2026. Current evidence indicates that highly sensitive platforms, including digital PCR, BEAMing, and next-generation sequencing, can detect clinically actionable alterations in genes such as PIK3CA, ESR1, TP53, ERBB2, AKT1, and BRCA1/2. ctDNA has demonstrated particular utility in identifying minimal residual disease, monitoring therapeutic response, detecting emerging resistance mechanisms, and guiding targeted treatment selection in advanced breast cancer. However, applications in early cancer detection, population screening, and artificial intelligence-assisted clinical decision-making remain investigational. Widespread clinical implementation is constrained by low ctDNA abundance in early-stage disease, analytical variability, limited assay standardization, and cost considerations. Continued technological innovation, prospective multicenter validation, standardized testing protocols, and evidence-based clinical guidelines are essential to fully integrate ctDNA into routine precision breast cancer care.

breast cancer↗
PubMed2002

The application of PET-MR image registration in the brain.

The coregistration in three-dimensional space of positron emission tomography (PET) and magnetic resonance (MR) image volumes has, over the last decade, become a matter of routine in the analysis of brain PET studies. The ability to objectively localize small regions of interest in PET using images more closely correlated to tissue structure has itself improved the effective resolution of PET. There are a number of highly effective software packages for image coregistration available in the public domain. Voxel-by-voxel coregistration, involving little or no intervention from the user can, on today's computing hardware, provide fast and accurate registration with little or no pre-processing and algorithms based on mutual information measures now seem to be the mathematical method of choice. Registration may be applied in a number of ways. Rigid body registration is used to match a single subject's brain scanned using either different imaging modalities or as serial scans with the same modality. Increasingly, this technique is being extended to studies of disease involving regional atrophy, where location and extent of tissue loss can be identified. Non-linear registration can be used to warp a subject's brain onto a template, atlas or other standardized guide. While numerous examples are available of the added value produced by image registration in the brain, similar examples are not yet available from registration in the torso, where the problem is much more complex. It is here that newly emerging hardware such as combined PET/CT scanners may prove their worth.

Algorithms↗
PubMed2001

Variation in skin reactivity inhalant allergens estimated by the end-point technique.

Skin prick testing is commonly used to diagnose IgE-mediated sensitization to allergens, whereas the longitudinal variability in positive/negative results can be used for clinical and epidemiological purposes. Few publications have investigated the longitudinal variability in skin reactivity, and most studies have concluded that seasonal changes in exposure to environmental allergens are paralleled by a change in skin reactivity. Our trial investigated the relationship between variations in skin reactivity and seasonal exposure to allergens in sensitized subjects, by use of a sensitive method-the end-point technique. Forty-three patients monosensitized to inhalant allergens were selected, and the skin prick end-point technique with serial 1:4 dilutions of standardized commercial allergens was used to assess skin reactivity. Twenty-two patients sensitized to pollens with a short pollination period were tested before and after the pollen season, whereas the other 21 patients sensitized to house dust mites or to a species with a long pollination period such as Parietaria were tested in the same month 12 months later. Patients tested with the end-point technique showed a large interindividual variability in skin reactivity. None of the patients in either group showed a decrease in skin sensitivity with time whereas 9 out of 43 showed no change and 34 out of 43 showed an increase (p < .0001). According to our data, skin reactivity increases in sensitized subjects over time, and this increase seems not to have a circannual rhythm related to the seasonal exposure to environmental allergens, since it can be detected both in pollen- and mite-sensitized patients after a 12-month interval.

Administration, Inhalation↗
PubMed1994

Importance of blood pressure control in the preservation of renal function.

End-stage renal disease has become a major and costly public health problem owing primarily to an accelerating incidence of renal failure from hypertension and diabetes. In both disease groups the primary problem appears to be persistent elevation of blood pressure, and there is evidence that early and effective blood pressure control arrests the renal damage and provides continuing protection to the kidney. It is recommended that the blood pressure be controlled to levels below 150/95 mm Hg for essential hypertension and below 140/85 mm Hg for the hypertensive diabetic. Serial monitoring of renal function can be done with a graph of reciprocal (1/serum creatinine) values of annual serum creatinine measurements, particularly in groups at increased risk for end-stage renal disease. High-risk groups include blacks, older individuals, and those with serum creatinine levels > or = 1.5 micrograms/dL.

Blood Pressure↗
PubMed1997

Eight years of "Prostate Cancer Awareness Week": lessons in screening and early detection. Prostate Cancer Education Council.

BACKGROUND: Prostate Cancer Awareness Week began in 1989 to raise public awareness of the disease and impact on its clinical dynamics. Prior to 1990, prostate carcinoma was usually diagnosed in symptomatic men as advanced and ipso facto incurable. METHODS: A 5-year longitudinal study of screening and early detection was initiated in 1992, involving 250 centers that tested over 50,000 men annually. The study analyzed the following: 1) the efficacy of digital rectal examination and prostate specific antigen (PSA) tests for the early detection of prostate carcinoma, 2) the impact of serial screening on stage of disease at diagnosis and cancer detection, 3) age and race specific reference ranges for PSA, 4) prostate carcinoma risk factors, and 5) psychosocial variables that influence the appropriateness and acceptability of both screening and treatment. RESULTS: Community-based screening for prostate carcinoma is as effective as programs conducted at academic centers, but annual testing may not be necessary for all men. Participants in community screening programs may require more prescreening information and education regarding the potential risks and benefits of screening, and also regarding the cascade of diagnostic and treatment decisions that follow an abnormal digital rectal examination or an elevated PSA finding. CONCLUSIONS: Community-based prostate carcinoma screening programs have contributed to the shift in the diagnosis of prostate carcinoma at an earlier stage. They provide data that are useful in studying the natural course of prostate carcinoma and in designing studies of the effect that prostate carcinoma screening has on mortality from the disease.

Community Medicine↗
PubMed2002

Ketamine impairs multiple cognitive domains in rhesus monkeys.

Available evidence suggests that recreational use and abuse of the dissociative anaesthetic ketamine is increasing. Characterization of the cognitive risks of ketamine exposure contributes substantially to understanding this growing public health threat. Although prior human studies demonstrate that ketamine impairs a range of cognitive skills, investigation in nonhuman models permits more precise exploration of neurochemical mechanisms which may underlie detrimental behavioral effects. Adult male rhesus monkeys (N=7) were trained on a neuropsychological battery including tests of memory (delayed match-to-sample, DMS; self-ordered spatial search, SOSS), reaction time (RT), reinforcer efficacy and sustained attention (progressive ratio, PR) and fine motor coordination (bimanual motor skill, BMS). Battery performance was then serially challenged with acute doses of ketamine (0.3, 1.0, 1.78 mg/kg IM). Ketamine impaired DMS and SOSS in a dose x difficulty dependent manner with the most difficult task conditions disrupted at the 1.0 and 1.78 mg/kg doses. Thus, both visual recognition memory and working memory indices were affected. Ketamine also slowed RT and BMS performance and interfered with PR performance at the 1.78 mg/kg dose. Overall the present findings confirm that ketamine interferes with multiple aspects of cognition at subanesthetic doses in monkeys.

Anesthetics, Dissociative↗
PubMed2004

Serial analysis of gene expression in sinusoidal endothelial cells from normal and injured mouse liver.

Here we describe gene expression profiles of mouse liver sinusoidal endothelial cells (LSECs) revealed by serial analysis of gene expression (SAGE). We prepared SAGE libraries of LSECs from normal and injured liver by CCl(4) administration, and we obtained 32,867 tags from normal and 37,493 tags from injured liver, representing 6011 unique transcripts. CCl(4) administration upregulated several genes related to cell growth and differentiation (Cdkn1a, Irf1, Il4ra, etc.), whereas it downregulated genes related to cell growth or protein transport (Kdr, Igfbp4, Ap1b1, etc.). To identify genes preferentially expressed in LSEC, we compared our SAGE libraries with 77 publicly available libraries generated from various mouse tissues and cell lines. We identified 23 genes, including Stab2 and uncharacterized genes, as possible markers for LSEC, which will be useful to analyze the specific role for LSECs in normal as well as regenerating liver.

Animals↗
PubMed2002

Evolution of drug resistance in Candida albicans.

The widespread deployment of antimicrobial agents in medicine and agriculture is nearly always followed by the evolution of resistance to these agents in the pathogen. With the limited availability of antifungal drugs and the increasing incidence of opportunistic fungal infections, the emergence of drug resistance in fungal pathogens poses a serious public health concern. Antifungal drug resistance has been studied most extensively with the yeast Candida albicans owing to its importance as an opportunistic pathogen and its experimental tractability relative to other medically important fungal pathogens. The emergence of antifungal drug resistance is an evolutionary process that proceeds on temporal, spatial, and genomic scales. This process can be observed through epidemiological studies of patients and through population-genetic studies of pathogen populations. Population-genetic studies rely on sampling of the pathogen in patient populations, serial isolations of the pathogen from individual patients, or experimental evolution of the pathogen in nutrient media or in animal models. Predicting the evolution of drug resistance is fundamental to prolonging the efficacy of existing drugs and to strategically developing and deploying novel drugs.

Antifungal Agents↗
PubMed2006

Corpse dismemberment in the material collected by the Department of Forensic Medicine, Cracow, Poland.

In this study, we present 23 cases of dismembered bodies examined by the Cracow Department of Forensic Medicine in 1968-2005 period. Presented material includes 17 instances of defensive mutilation, three instances of offensive mutilation and two cases when dismemberment (decapitation) was a direct cause of death. One case is hard to classified, the perpetrator dissected free skin from the all torso. Analysis of all presented cases and other publications concentrating on the problem of dismemberment gave us the possibility to perform some conclusions. Apart from rare cases of necrophilia, the victim of dismemberment is always a victim of homicide. Homicides ending with corpse dismemberment are most commonly committed by a person close to, or at least acquainted with the victim and they are performed at the site of homicide, generally in the place inhabited by the victim, the perpetrator or shared by both. Such instances are generally not planned by the perpetrator and rarely serial in character.

Cadaver↗
PubMed2006

Comparison of growth patterns of acoustic neuromas with and without radiosurgery.

OBJECTIVE: To compare the natural history of acoustic neuroma growth to the reported growth rate of acoustic neuromas after radiosurgical therapy, a retrospective review and meta-analysis of the literature was performed. The retrospective review was of one hundred eleven patients (average age, 71 yr) who chose to have their acoustic neuromas managed conservatively in our institution. These patients underwent serial magnetic resonance imaging for assessment of tumor growth for an average period of 38 months. Growth patterns if these untreated tumors were compared to that of radiosurgically treated acoustic neuromas reported in the literature. DATA SOURCES: The English-language literature on the topic was searched systematically by Medline and Pubmed using the following key words: acoustic neuroma, vestibular schwannoma, conservative management, conservative treatment, nonsurgical, age, elderly, growth, observation, untreated, radio-surgery, gamma knife, 13 Gy and 12 Gy. There were no limits to the year of publication. STUDY SELECTION: Articles that fulfilled inclusion criteria (methods) were studied in detail. DATA EXTRACTION: All the articles described in the study selection were used in the review. CONCLUSION: The average growth rate of the untreated tumors was 0.7 +/- 1.4 mm/yr. Eighty-two percent grew less than 1 mm/yr, whereas 18% grew equal to or more than 1 mm/yr. Thirteen percent grew more than 2 mm/yr, with growth being noted at an average of 2.2 years after diagnosis. This represents an 87% control rate if tumor control rate is defined as less than 2-mm growth/yr. Meta-analysis indicates that tumor control rates range in the radiosurgical literature from 86% to 100%. The mean follow-up periods in the radiosurgical literature are generally not reported. Tumor control is not uniformly defined. Based on the results of this study, there is no discernable significant difference between growth patterns of untreated acoustic neuromas and those treated radiosurgically. To establish a significant difference, longer-term follow-up studies with larger sample sizes and tumor control rates are needed. Tumor control should be defined as zero growth.

Adult↗
PubMed2006

A population-based and longitudinal study of sexual behavior and multidrug-resistant HIV among patients in clinical care.

BACKGROUND: Population-based and longitudinal information regarding sexual risk behavior among patients with multidrug resistant (MDR) HIV and their sexual partners is of great public health and clinical importance. OBJECTIVE: To characterize the HIV sexual risk behaviors of patients with and without drug-resistant HIV in the clinical care setting over time. MEASUREMENTS: 393 HIV-positive patients completed questionnaires of self-reported sexual risk behaviors at approximate 6-month intervals extending over 24 months. HIV viral load and genotypic drug resistance obtained during the same time points were matched to the behavioral data. Multidrug resistance was defined as having resistance to 2 or 3 antiretroviral (ARV) drug classes. RESULTS: In serial cross-sectional analyses, 393 patients (44% female and 79% heterosexual) contributed 919 matched behavioral and virologic results over the 24 months of data collection. Of these, 250 patients (64%) reported having sex during at least 1 survey period resulting in greater than 10,000 sexual events with more than 1000 partners. Unprotected sexual behavior was reported by 45% of sexually active patients, resulting in 34% of all sex events that exposed 29% of all partners. Of these patients with unprotected sexual events, 31% had HIV drug resistance--11.6% with resistance to 2 classes of ARVs (2-class), and 1.8% with 3-class ARV resistance at the time of a sexual risk event. Close to 1000 or 28% of all unprotected sexual events involved resistant strains (11% of these with resistance to 2 classes and 0.2% with 3-class resistance, exposing 20% of unprotected sexual partners to resistant HIV (8% to 2-class and 0.6% to 3-class resistance). In longitudinal analysis among the 78 patients who reported a cumulative total of 12 months of sexual history and had resistance testing, 38% reported engaging in unprotected sexual behavior. There was substantial and complex variation in the distribution of unprotected sexual events and in the detection of resistance over time. CONCLUSION: In this study of HIV sexual risk and resistance over time among HIV-infected patients in clinical care, a substantial proportion engaged in unprotected sex and had drug-resistant HIV, frequently exposing partners to 1- or 2-class resistant HIV strains. However, relatively few exposures involved 3-class resistance. The dynamics of sexual risk behavior and HIV drug resistance are complex and vary over time and urgently require both general and targeted interventions to reduce transmission of resistant HIV.

Adult↗
PubMed1995

A 3D digital map of rat brain.

A three dimensional (3D) computerized map of rat brain anatomy created with digital imaging techniques is described. Six male Sprague-Dawley rats, weighing 270-320 g, were used in the generation of this atlas. Their heads were frozen, and closely spaced cryosectional images were digitally captured. Each serial data set was organized into a digital volume, reoriented into a flat skull position, and brought into register with each other. A volume representative of the group following registration was chosen based on its anatomic correspondence with the other specimens as measured by image correlation coefficients and landmark matching. Mean positions of lambda, bregma, and the interaural plane of the group within the common coordinate system were used to transform the representative volume into a 3D map of rat neuroanatomy. images reconstructed from this 3D map are available to the public via Internet with an anonymous file transfer protocol (FTP) and World Wide Web. A complete description of the digital map is provided in a comprehensive set of sagittal planes (up to 0.031 mm spacing) containing stereotaxic reference grids. Sets of coronal and horizontal planes, resampled at the same increment, also are included. Specific anatomic features are identified in a second collection of images. Stylized anatomic boundaries and structural labels were incorporated into selected orthogonal planes. Electronic sharing and interactive use are benefits afforded by a digital format, but the foremost advantage of this 3D map is its whole brain integrated representation of rat in situ neuroanatomy.

Animals↗
PubMed2002

Endogenous lipoproteins impact the response to endotoxin in humans.

OBJECTIVE: To determine whether endogenous lipoproteins can abrogate the host response to lipopolysaccharide (LPS) in vivo. DESIGN: Randomized, placebo-controlled study. SETTING: Urban public hospital with academic affiliation. SUBJECTS: Eighteen healthy, normolipidemic, normal weight volunteers, 21-35 yrs of age. INTERVENTIONS: Fasting and postprandial (hypertriglyceridemic) subjects were injected with endotoxin (LPS, Lot EC-5, 4 ng/kg = 20 endotoxin units/kg) as either a bolus or following preincubation of the LPS with autologous whole blood vs. saline. In addition, LPS-induced cytokine production was determined ex vivo to examine the capacity of fasting vs. hypertriglyceridemic whole blood to attenuate the effect of large, potentially lethal concentrations of LPS in humans. MEASUREMENTS: Vital signs were recorded and serial blood samples analyzed for changes in white blood cell count, cytokine, and stress hormone levels over 24 hrs. The distribution of lipoproteins in fasting and postprandial blood after preincubation was determined using 125I-LPS. MAIN RESULTS: Endogenous lipoproteins abrogated the host response to LPS in vivo, but only after preincubation with the LPS. Peak oral temperature (p < .05) and white blood cell count (p < .05), and plasma tumor necrosis factor (TNF)-alpha (p < .01) and adrenocorticotropic hormone levels (p < .03) were significantly reduced in volunteers injected with LPS preincubated with whole blood vs. LPS preincubated with saline. Approximately 80% of the LPS was bound to lipoproteins after preincubation with either fasting or hypertriglyceridemic blood. Thus, protection was associated with lipoprotein binding. In addition, hypertriglyceridemic but not fasting blood inhibited the ex vivo TNF-alpha response to large, highly toxic doses of LPS (p < .05). Without the preincubation of lipoproteins with LPS, there was a trend for an exaggerated clinical and TNF-alpha response in the hypertriglyceridemic subjects. CONCLUSION: Preincubation of LPS with whole blood promotes lipoprotein-LPS binding and is associated with an attenuated response to this toxic macromolecule. Although the clinical relevance of these data requires further elucidation, our results continue to support a lipid-based therapeutic strategy to combat gram-negative sepsis.

Acute-Phase Proteins↗
PubMed1985

Cost of orthopedic injuries sustained in motorcycle accidents.

Fifty-one serial admissions to the orthopedic services at the University of California, Davis, Medical Center, Sacramento, for motorcycle accident trauma with open fractures were reviewed. Fifty-five percent of those tested were alcohol intoxicated at the time of admission. Seventy-five percent carried no insurance of any kind, and for the total group, 72% of the cost of acute hospitalization (+17,704 per patient) was paid by the state of California, with an additional 10% paid by other tax-based sources. Care of motorcycle trauma consumes a substantial portion of public health care funds in California. This could be reduced by legislative action concerning helmet use, licensing, and rigid enforcement of compulsory insurance.

Accidents, Traffic↗
PubMed2004

Regulating opioid prescribing through prescription monitoring programs: balancing drug diversion and treatment of pain.

Social policies have evolved to address the associated concerns related to the public health crises of drug abuse and undertreated pain. Prescription monitoring programs (PMPs) have been used for many years in this effort but are undergoing re-evaluation and restructuring in light of changes in technology as well as changes in our understanding of the collateral impact of such programs. We reviewed the state of PMPs in the United States and highlighted recent changes in these programs that have occurred nationally. The current changes occurring in California, with the most physicians of any U.S. state as well as the oldest triplicate-based serialized prescription program, are reviewed, with focus on the transition to tamper-resistant prescriptions that use security paper forms. Future trends for PMPs are described, including the potential for widespread use of electronic prescribing, which is gaining favor with the Drug Enforcement Agency.

Analgesics, Opioid↗
PubMed1991

Human immunodeficiency virus and the acquired immunodeficiency syndrome in obstetrics.

Human immunodeficiency virus infections complicating pregnancy have become a major public health problem worldwide. Infected women may transmit the virus to offspring and longitudinal studies have reported this risk to be from 13% to 40%. Differences in reported transmission risks are likely to be related to maternal plasma viremia, maternal immunologic responses, or both. Studies of antiretroviral therapy and immune based therapy to reduce the risk of perinatal transmission are needed. In addition to these fetal concerns, management in pregnancy needs to address maternal health-care needs and health care workers' concerns regarding the risk of occupational exposure. Appropriate maternal management includes serial assessments of maternal T-lymphocyte function and consideration of prophylactic and therapeutic treatment options proven effective in nonpregnant adults.

Ethnicity↗