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Objectives: To survey international regulatory frameworks that serve to protect privacy of personal data as a human right as well as to review the literature regarding privacy protections and data ownership in mobile health (mHealth) technologies between January 1, 2016 and June 1, 2019 in order to identify common themes.Methods: We performed a review of relevant literature available in English published between January 1, 2016 and June 1, 2019 from databases including PubMed, Google Scholar, and Web of Science, as well as relevant legislative background material. Articles out of scope (as detailed below) were eliminated. We categorized the remaining pool of articles and discrete themes were identified, specifically: concerns around data transmission and storage, including data ownership and the ability to re-identify previously de-identified data; issues with user consent (including the availability of appropriate privacy policies) and access control; and the changing culture and variable global attitudes toward privacy of health data.Results: Recent literature demonstrates that the security of mHealth data storage and transmission remains of wide concern, and aggregated data that were previously considered “de-identified” have now been demonstrated to be re-identifiable. Consumer-informed consent may be lacking with regard to mHealth applications due to the absence of a privacy policy and/or to text that is too complex and lengthy for most users to comprehend. The literature surveyed emphasizes improved access control strategies. This survey also illustrates a wide variety of global user perceptions regarding health data privacy.Conclusion: The international regulatory framework that serves to protect privacy of personal data as a human right is diverse. Given the challenges legislators face to keep up with rapidly advancing technology, we introduce the concept of a “healthcare fiduciary” to serve the best interest of data subjects in the current environment.

Graduate students are developing skills in scientific communication, research, and various other specified trainings. However, adequate resources for these students are not always available at their home institution. Educational outreach programs are often discussed in relation to secondary education. The potential to expand these types of programs to the post-secondary and graduate levels of education would represent a potential benefit to the students, scientists, and universities involved in the exchange. In such programs, graduate students would participate in an exchange with other universities to address deficits introduced by a lack of resources. This educational experience in a new setting would allow exposure to techniques and ideals otherwise inaccessible to the student. The objective of this observational case study was to evaluate the relevance and value of graduate exchange as an educational outreach model in graduate education. In this case study, a graduate student from Tarleton State University’s Department of Animal Science and Veterinary Technology was supported to study for a period of three weeks in the University of Georgia’s Parasitology Laboratory. This exchange was established to teach in vitro techniques related to the student’s graduate research. The student was able to gain valuable experience in laboratory techniques that aided in personal and professional growth while also expanding the capabilities of the home institution through training exercises conducted on return to campus. In addition to expansion of research capacity, the student was able to serve as an ambassador for the home institution, thereby enabling a more fluid exchange of ideas through student recruitment. Qualitative results from this case study would indicate that similar educational outreach opportunities are valuable components of graduate education and serve as an example for development in future graduate programs.

TAE Technologies' research is devoted to producing high temperature, stable, long-lived field-reversed configuration (FRC) plasmas by neutral-beam injection (NBI) and edge biasing/control. The newly constructed C-2W experimental device (also called "Norman") is the world's largest compact-toroid (CT) device, which has several key upgrades from the preceding C-2U device such as higher input power and longer pulse duration of the NBI system as well as installation of inner divertors with upgraded electrode biasing systems. Initial C-2W experiments have successfully demonstrated a robust FRC formation and its translation into the confinement vessel through the newly installed inner divertor with adequate guide magnetic field. They also produced dramatically improved initial FRC states with higher plasma temperatures (Te ~250+ eV; total electron and ion temperature g1.5 keV, based on pressure balance) and more trapped flux (up to ~15 mWb, based on rigid-rotor model) inside the FRC immediately after the merger of collided two CTs in the confinement section. As for effective edge control on FRC stabilization, a number of edge biasing schemes have been tried via open field-lines, in which concentric electrodes located in both inner and outer divertors as well as end-on plasma guns are electrically biased independently. As a result of effective outer-divertor electrode biasing alone, FRC plasma diamagnetism duration has reached up to ~9 ms which is equivalent to C-2U plasma duration. Magnetic field flaring/expansion in both inner and outer divertors plays an important role in creating a thermal insulation on open field-lines to reduce a loss rate of electrons, which leads to improvement of the edge and core FRC confinement properties. Experimental campaign with inner-divertor magnetic-field flaring has just commenced and early result indicates that electron temperature of the merged FRC stays relatively high and increases for a short period of time, presumably by NBI and ExB heating.

Schizophrenia is a chronic, disabling neuropsychiatric disorder characterised by positive, negative and cognitive symptoms. The aetiology is not known, although genetic, imaging and pathological studies have implicated both neurodevelopmental and neurodegenerative processes. The substantia nigra is a basal ganglia nucleus responsible for the production of dopamine and projection of dopaminergic neurons to the striatum. The substantia nigra is implicated in schizophrenia as dopamine has been heavily implicated in the dopamine hypothesis of schizophrenia and the prevalent psychotic symptoms and the monoamine theory of depression, and is a target for the development of new therapies. Studies into the major dopamine delivery pathways in the brain will therefore provide a strong base in improving knowledge of these psychiatric disorders. This post-mortem study examines the cytoarchitecture of dopaminergic neurons of the substantia nigra in schizophrenia (n = 12) and depression (n = 13) compared to matched controls (n = 13). Measures of nucleolar volume, nuclear length and nuclear area were taken in patients with chronic schizophrenia and major depressive disorder against matched controls. Astrocyte density was decreased in schizophrenia compared to controls (p = 0.030), with no change in oligodendrocyte density observed. Significantly increased nuclear cross-sectional area (p = 0.017) and length (p = 0.021), and increased nucleolar volume (p = 0.037) in dopaminergic neurons were observed in schizophrenia patients compared with controls, suggesting nuclear pleomorphic changes. No changes were observed in depression cases compared to control group. These changes may reflect pathological alterations in gene expression, neuronal structure and function in schizophrenia.

North American shale oil producers find themselves in the spotlight. Before 2015, much focus was placed on the miraculous growth of U.S. crude production, which ramped up by 1 million barrels per day (MMBbl/d) every year for five consecutive years, a phenomenon often characterized as the "shale boom". But, heading into 2015, these same producers were hit particularly hard by the sharp and rapid decline in crude oil prices. In an attempt to better understand how North American production has reacted to the fall of oil prices, this paper begins with a high-level overview of the key value drivers behind the shale boom. It aims to explain how past drilling activities, ongoing rig count changes and drilled but uncompleted wells influence current and future shale oil production. Although the dynamics of crude supply and demand are highly unpredictable, this paper identifies underlying themes in the North American oil and gas industry that continue to prevail during a highly volatile market.

PURPOSE OF REVIEW: Munchausen syndrome by proxy (MBP) is a complicated form of child maltreatment. Difficulties remain in properly defining the condition, as well as in detection and differentiation from organic illness. This review will discuss the epidemiology and diagnosis of MBP, as well as the role of the physician in sorting out these cases. RECENT FINDINGS: Several recent case studies, including two in which children were diagnosed with celiac disease, add to our knowledge of the protean manifestations of MBP. There is growth in our understanding of how sudden infant death syndrome (SIDS) and the symptom complex seen in acute life-threatening events (ALTEs) may in fact represent manifestations of MBP. Recent legal issues in the United Kingdom pose concern for all physicians engaged in child protection work. SUMMARY: In spite of these challenges, the high mortality and recidivism rates associated with MBP make it imperative that pediatricians be familiar with the condition, the subtle signs and symptoms with which it may present, and methods to best protect the children in their care. Language: en

Five batches of aerobically packaged minced beef from Friesian cattle were irradiated at 0, 1, 2, 3 or 4 kGy using a (60)Co irradiation source. The five batches were as follows: non-supplemented (C), dietary α-tocopheryl acetate supplemented (S), α-tocopheryl acetate supplemented with water soluble rosemary extract added after mincing (Rw), α-tocopheryl acetate supplemented with oil soluble rosemary extract added after mincing (Ro) and α-tocopheryl acetate supplemented with water and oil soluble rosemary extracts added after mincing (R). Incorporation of antioxidants resulted in better retention of colour. Irradiation at 4 kGy increased Hunter 'a' values up to day 4 with α-tocopheryl acetate supplementation and up to day 6 when rosemary extracts were added. Irradiation at 4 kGy increased Hunter 'b' values on days 4, 6 and 8 in the control samples. Antioxidants decreased metmyoglobin values on day 0 and day 2 for non-irradiated (0 kGy) samples and for the entire display period for irradiated samples. Antioxidants increased the oxymyoglobin values up to day 4 for the 1, 2 and 3 kGy beef samples and over the entire display period for the 4 kGy samples. TBARS values for each treatment group increased with increasing irradiation dose. α-Tocopheryl acetate supplemented samples had lower TBARS values than control samples at all irradiation doses. The levels of α-tocopherol in samples on day 0 decreased with increasing irradiation dose for the (C) and (S) samples. However, levels of α-tocopherol in samples on day 0 increased with increasing irradiation dose for Ro, Rw and R samples. All antioxidant treatments were effective at inhibiting lipid peroxidation even at the highest irradiation dose applied. Irradiation caused a significant reduction in the polyunsaturated fatty acid (PUFA) content, mainly in C18:2 after storage at 40°C under fluorescent light for 8 days.

Heifers (n=10) were randomly selected from the slaughter line of a local factory each month for a period of 21 months. Rib steak (sampled at the 10th rib) from the left side of each carcass was taken for analysis. The cattle breeds selected during this study were Friesian, Hereford and Charolais. The mean weight of the left side for all carcasses was 146.6 (S.E.M.= 1.0kg). Graded carcasses selected for sampling during this trial were classified using the EUROP scale and the specific heifer grades chosen were factory grades EO4L and EO4H. Initial Hunter 'a' values (on the day of arrival in the laboratory) of rib steak from heifers finished between November and March (overwintered) were significantly (P0.001) higher than Hunter 'a' values from heifers finished between April and October (pastured). After storage at 4 °C under simulated retail display conditions for 6 days, the Hunter 'a' values for overwintered samples were also significantly (P0.001) greater than those for pastured samples. Breed also had an effect on the colour of the meat. After storage for 6 days, Hunter 'a' values of rib steak from Charolais were significantly (P0.05) higher than either Friesian or Hereford. Pastured heifers had significantly (P0.05) higher levels of the monounsaturated fatty acid C16.1 in the total lipid fraction of rib steak (neutral and polar) than samples taken from overwintered heifers. Pastured heifers had significantly (P0.01) higher levels of the polyunsaturated fatty acid (PUFA) C18.3 in the phospholipid fraction than those from overwintered cattle. However, Hereford had significantly (P0.05) higher levels of C14.0, C16.1 and C18.0 in the phospholipid fraction than those found in Friesian and Charolais. The level of α-tocopherol in the muscle was not affected by either pasturing/overwintering or breed. However, Continental breeds had significantly (P0.05) higher levels of α-tocopherol in adipose tissue than Friesian.

The study objectives, based on federal and state legislative language, were to objectively define symptoms and signs commonly agreed on by "prudent laypersons" as "emergency medical conditions." After comprehensive tabulation of symptom classifications from the International Classification of Diseases (ICD-9), we performed a survey of nonmedical laypersons. Data analysis included descriptive statistics, proportional calculations, and 95% confidence intervals. A minority of symptoms and signs (25/87, 29%) were considered emergency medical conditions by more than half of nonmedical survey respondents who were self-defined as prudent laypersons. The leading conditions deemed emergencies were loss of consciousness, seizure, no recognition of one side of the body, paralysis, shock, gangrene, coughing blood, trouble breathing, chest pain, and choking. Pain, except for renal colic or chest pain, was not considered an emergency. No symptoms or signs specifically related to gynecologic disorders were considered emergencies. Most symptoms and signs tabulated in the diagnostic coding manual, ICD-9, are not considered emergency medical conditions by self-designated prudent laypersons. These include many conditions that are commonly investigated and treated in the emergency department setting. Use of the prudent layperson standard for reimbursable emergency health services may not reflect the actual scope of symptoms necessitating emergency care.

Lipid oxidation is one of the main factors limiting the quality and acceptability of meats and meat products. Oxidative damage to lipids occurs in the living animal because of an imbalance between the production of reactive oxygen species and the animal's defence mechanisms. This may be brought about by a high intake of oxidized lipids or poly-unsaturated fatty acids, or a low intake of nutrients involved in the antioxidant defence system. Damage to lipids may be accentuated in the immediate post-slaughter period and, in particular, during handling, processing, storage and cooking. In recent years, pressure to reduce artificial additive use in foods has led to attempts to increase meat stability by dietary strategies. These include supplementation of animal diets with vitamin E, ascorbic acid, or carotenoids, or withdrawal of trace mineral supplements. Dietary vitamin E supplementation reduces lipid and myoglobin oxidation, and, in certain situations, drip losses in meats. However, vitamin C supplementation appears to have little, if any, beneficial effects on meat stability. The effect of feeding higher levels of carotenoids on meat stability requires further study. Some studies have demonstrated that reducing the iron and copper content of feeds improves meat stability. Post-slaughter carnosine addition may be an effective means of improving lipid stability in processed meats, perhaps in combination with dietary vitamin E supplementation.

Lipid oxidation is one of the main factors limiting the quality and acceptability of meats and meat products. Oxidative damage to lipids occurs in the living animal because of an imbalance between the production of reactive oxygen species and the animal's defence mechanisms. This may be brought about by a high intake of oxidized lipids or poly-unsaturated fatty acids, or a low intake of nutrients involved in the antioxidant defence system. Damage to lipids may be accentuated in the immediate post-slaughter period and, in particular, during handling, processing, storage and cooking. In recent years, pressure to reduce artificial additive use in foods has led to attempts to increase meat stability by dietary strategies. These include supplementation of animal diets with vitamin E, ascorbic acid, or carotenoids, or withdrawal of trace mineral supplements. Dietary vitamin E supplementation reduces lipid and myoglobin oxidation, and, in certain situations, drip losses in meats. However, vitamin C supplementation appears to have little, if any, beneficial effects on meat stability. The effect of feeding higher levels of carotenoids on meat stability requires further study. Some studies have demonstrated that reducing the iron and copper content of feeds improves meat stability. Post-slaughter carnosine addition may be an effective means of improving lipid stability in processed meats, perhaps in combination with dietary vitamin E supplementation.

A basic phosphoprotein defined by a monoclonal antibody named AF5 was found to be highly abundant in human hepatocellular carcinoma by Western immunoblotting. Under the same conditions, the levels of this phosphoprotein were low or undetectable in normal liver extracts. The AF5 antibody was used to screen a cDNA expression library of a human hepatoma cell line named FOCUS. A 960-base-pair cDNA was isolated and found to be a partial cDNA encoding the human protein-tyrosine kinase substrate p36, also known as lipocortin II. p36 expression was highly abundant in hepatocellular carcinomas at both the transcript and protein levels. Its expression was not induced significantly during rat liver regeneration following a partial hepatectomy. These results suggest that the induction of p36 expression is associated with malignant transformation of hepatocytes. p36 was previously shown to be phosphorylated upon transformation of normal fibroblasts by retroviral oncogenes without significant modulation of expression. We report here the initial description of the association of increased p36 expression with malignant transformation.

The effects of three preslaughter diets on heifer beef quality were investigated. Heifers (n = 45) were divided into three groups and fed for ad libitum consumption either maize silage, grass silage, or a 50:50 mixture of maize silage and grass silage. Meat quality was determined by measuring color, lipid oxidation, alpha-tocopherol levels, and fatty acid composition. Beef from the maize silage group had poorest color stability (P < 0.05), whereas beef from the grass silage diet had best (P < 0.05) color stability. The visual panel least preferred the maize silage group after 2 or more days of display, and lipid oxidation was significantly (P < 0.001) higher in this group compared to the 50:50 maize:grass silage and grass silage groups. There was a significant (P < 0.001) difference in the alpha-tocopherol levels detected in the meat from the three dietary groups. Alpha-tocopherol levels increased in the order: maize silage < 50:50 maize:grass silage < grass silage, at levels of 2.08, 2.95, and 3.84 microg/g meat, respectively. Fatty acid analysis indicated 18:3 was significantly (P < 0.001) lower in the maize silage-fed group than in the maize:grass silage and grass silage groups. However, 18:3 was significantly (P < 0.001) higher in the grass silage group than in the other two groups. There were no significant differences in all other fatty acids among the three dietary groups. It was concluded that beef from grass silage-fed animals had better overall quality in terms of color, lipid oxidation, and alpha-tocopherol levels than beef from maize silage fed animals.

Study objectives To determine whether an association exists between aortic calcification viewed on plain chest radiography and coronary artery disease. Methods Retrospective review of all chest radiographs obtained from consecutive patients undergoing coronary angiography at a primary cardiac center during 1999. Plain chest radiographs were reviewed by blinded radiologists, and interobserver consistency was measured. The presence or absence of aortic arch calcification was abstracted and compared with the results of coronary angiography. Results Of 654 cases, 329 of 360 patients with aortic arch calcification vs 241 of 294 patients without aortic arch calcification had coronary artery disease demonstrated on angiography. The 9% absolute difference in proportions was significant (p = 0.0003). The relative risk (measured by risk ratio) was 1.11 (95% confidence interval, 1.05 to 1.19). Conclusion Several objective signs ( eg , hypertension, hyperlipidemia, and ECG changes) have been associated previously with the presence of coronary artery disease. This study further suggests an association between coronary disease and aortic arch calcification on plain chest radiography. These results may assist primary-care providers performing routine health assessments as well as emergency practitioners evaluating patients with potential angina.

The 1999/2000 winter demands on the NHS have once again highlighted deficits in UK critical care provision (Daily Telegraph, 2000; London Evening Standard, 2000) Recent years have seen the development of the role of health care support workers in the NHS; some critical care units now employ health care support workers This research examined the views of critical care unit staff on the introduction of health care support workers into the critical care unit It is concluded that the role is viable within the setting of this study A framework is outlined that could form the basis for a critical care health care support worker training programme

A randomized, double-blind trial was conducted to compare the efficacy of a high-dose versus standard-dose hepatitis B vaccine in alcoholic patients.One hundred ten alcoholic patients were randomized to either receive the standard dose (20 micrograms at 0.1, and 6 months) or a high dose (40 micrograms at 0, 1, 2, and 6 months) of recombinant hepatitis B vaccine (Engerix-B). Patients were monitored for relapse of drinking using self-report, serial serum carbohydrate deficient transferrin, and collateral verification. The final titer of antibody to hepatitis B surface antigen (anti-HBs) was obtained 12 months after the first vaccine dose; a seroconversion was defined as a titer greater than 10 mlU/ml.One hundred subjects completed the study; 10 of these had clinical or pathological evidence of cirrhosis. Thirty-six out of 48 (75%) of patients administered the high-dose regimen seroconverted compared with 24 of 52 (46%) in the standard dose group (P0.005). The mean anti-HBs titer of the high dose group was significantly greater than of the standard dose group (76.4 versus 39.4 mlU/ml, P0.01). Logistic regression demonstrated a significant effect on seroconversion for the vaccine dose (P0.005) and serum albumin (P = 0.05) but not for the other variables such as race, age, drinking during the study, serum creatinine, arm muscle circumference, and cirrhosis.A high- and accelerated-dose regimen of hepatitis B improves the serological response in alcoholic patients. This regimen (currently recommended for hemodialysis patients) should now also be considered for patients with a history of alcoholism.

This study assessed speech perception benefits for three congenitally deaf adolescents who used an electrotactile speech processor (Tickle Talker(TM)) and subsequently went on to use a Nucleus Minisystem 22 cochlear implant. Both devices provided significant and comparable benefits for all children in the device plus lipreading condition. All children benefited from the additional information provided by either the Tickle Talker(TM) or the cochlear implant, and were able to perceive speech information with these devices that was not available through either aided residual hearing or lipreading. None of the three children were able to understand open-set words or sentences using either hearing aids alone or Tickle Talker(TM) alone, without the aid of lipreading. Two of the children showed significant open-set speech perception benefits while using their cochlear implant alone.

Previous studies have suggested an association of viral hepatitis with alcoholism, although the role of confounding risk factors (e.g. i.v. drug use) has not been adequately excluded. We therefore compared the seroprevalences of hepatitis B and C in alcoholic patients to that of a nonalcoholic control group.Hepatitis B surface antigen, hepatitis B core antibody, hepatitis B surface antibody, and hepatitis C virus antibody testing (second generation ELISA and a confirmatory recombinant immunoblot assay) was performed in 150 consecutive alcoholics admitted for detoxification and in 166 randomly selected patients attending a general medical clinic who were screened for alcoholism.Hepatitis B and C seropositivities in actively drinking alcoholics are 49.3 and 35.3%, respectively, and were significantly associated with a history of i.v. drug abuse. Out of 166 general medicine clinics patients, 93 were classified as nonalcoholic (by both self-report and collateral verification), 46 patients had a history of alcoholism , and 27 were indeterminate. In the subgroup of patients without known viral hepatitis risk factors, there was no significant difference in hepatitis B seropositivity among nonalcoholic general medicine clinic patients, alcoholic general medicine clinic patients, and alcoholic patients admitted for detoxification (22.1%, 30.3%, and 27.6%, respectively). In contrast, anti-HCV recombinant immunoblot assay seropositivity in alcohol patients admitted for detoxification without risk factors was significantly greater than in nonalcoholic general medicine patients without risk factors (10 vs 0%, p0.01). Stepwise logistic regression analysis revealed that alcoholism requiring detoxification was a significant risk factor for hepatitis C but not for hepatitis B seropositivity.The increased seroprevalence of hepatitis C in actively drinking alcoholic patients without known risk factors suggests that alcoholism, in some way, is a predisposing factor for HCV infection.

We analyzed the status of retinoblastoma and p53 genes in 10 human hepatoma cell lines. Polyclonal anti-peptide antibodies generated against peptides homologous to COOH-terminal and leucine-zipper domains of the retinoblastoma protein allowed us to identify two cell lines (Hep 3B and FOCUS) with abnormal expression. The same cell lines have both lacked p53 expression. In contrast to the retinoblastoma gene, the expression of the p53 gene was abnormal in six additional cell lines. Indeed, only the Hep G2 hepatoblastoma cell line (and its derivative Hep G2/2215) appeared to have normal p53 and retinoblastoma gene expression. Our studies indicate that p53 abnormalities are common but retinoblastoma gene aberrations are rare in human hepatoma cell lines.

To evaluate the relationship between hepatitis C viral infection and alcoholic liver disease.Case-comparison study.Bronx (NY) Veterans Affairs Medical Center.Forty-seven consecutive alcoholic patients undergoing diagnostic liver biopsy.Serum was obtained at the time of liver biopsy and assayed for antibodies to hepatitis C virus using enzyme-linked immunosorbent assay, recombinant immunoblot assay, and hepatitis C virus neutralization methods.Antibody to hepatitis C virus, as confirmed by the recombinant immunoblot assay, was strongly associated with the presence of portal and/or lobular inflammation (91% seropositivity) but was only present in 16% of patients without this histologic finding (P.001). In patients without portal or lobular hepatitis, recombinant immunoblot assay seropositivity was seen in 27% of patients with cirrhosis and 20% of patients with alcoholic hepatitis and was absent in patients with steatosis and/or perivenular fibrosis. In the subgroup of alcoholic patients who were without known risk factors for hepatitis C virus infection (ie, no history of intravenous drug use or blood transfusions), antibody to hepatitis C virus was present in 78% of subjects with portal and/or lobular hepatitis but was absent in those with other types of alcoholic liver disease. Finally, anti-hepatitis C virus-seropositive patients had a significantly greater mean necroinflammatory score as compared with anti-hepatitis C virus-seronegative alcoholic patients (2.1 vs 1.2; P.001). In contrast, there was no significant difference in the mean fibrosis score between the two groups.The presence of portal and/or lobular inflammation is strongly associated with antibodies to hepatitis C virus in alcoholic patients, even in the absence of known risk factors. This association indicates that hepatitis C virus is responsible, at least in part, for the portal and/or lobular hepatitis associated with alcoholic liver disease.

A 90-kDa phosphoprotein (p90) of the endoplasmic reticulum was identified by a monoclonal antibody generated against human hepatoma cells. Pulse-chase experiments with [32P]phosphate and [35S]methionine demonstrated that p90 formed both stable and transient complexes with other cellular proteins, suggesting its role as a molecular chaperone. This protein associates with heavy chains of major histocompatibility complex class I proteins, suggesting that it is the human homolog of the recently described 88-kDa protein that transiently associates with murine class I molecules in the endoplasmic reticulum. The p90 protein also associates in B lymphocytes with membrane immunoglobulin mu heavy chains and may serve as a chaperone for many membrane-bound polypeptides. A partial human p90 cDNA was cloned from a lambda gt11 expression library and identified as the human homolog of calnexin, a major canine calcium-binding protein found to be associated with the signal-sequence receptor in endoplasmic reticulum membranes.

This paper presents further preliminary results of a trial of the prophylaxis of sepsis in 165 patients undergoing vascular surgery. The efficacy and safety of a single dose of teicoplanin was examined and compared with three doses of cephradine plus metronidazole. No significant differences were detected in the prophylactic efficacy in either group. The first interim report indicated abnormalities in liver function, maximum at 7 days, in both groups. These findings are confirmed in this second interim report. Raised levels of GGT and alkaline phosphatase are more prominent in patients receiving teicoplanin. Liver function improved by 28 days, however, suggesting that any abnormality is transient.

There is little information regarding the molecular mechanisms of hepatocarcinogenesis. We studied the p53 gene at the DNA, RNA, and protein level in seven human hepatocellular carcinoma (HCC)-derived cell lines; six of seven showed p53 abnormalities. By Southern blotting, the p53 gene was found to be partially deleted in Hep 3B and rearranged in SK-HEP-1 cells. Transcripts of the p53 gene were undetectable in Hep 3B as well as in FOCUS cells that had no apparent deletion or rearrangement of the p53 gene. Immunoprecipitation after [35S]methionine labeling of HCC cells demonstrated that p53 protein was absent in Hep 3B and FOCUS and reduced in concentration in PLC/PRF/5 cells. p53 synthesized by Mahlavu cells showed a slower migration on SDS/polyacrylamide gels suggesting it was an abnormal protein. In Huh7 cells, p53 protein had a prolonged half-life leading to its accumulation in the nuclei; increased levels of p53 protein were also found by immunoblotting. The p53 gene and its expression appeared to be unaltered in the hepatoblastoma-derived Hep G2 cell line. We found that the loss of p53 expression did not occur as a late in vitro event in the FOCUS cell line because p53 protein was also nondetectable at an early passage. We conclude that the loss of p53 expression or the presence of abnormal forms of the protein are frequently associated with HCC cell lines. These observations suggest that alterations in p53 may be important events in the transformation of hepatocytes to the malignant phenotype.

13026 Background: ON-1910.Na is a new chemical entity, novel cell cycle inhibitor which arrests cells in G2/M, affects phosphorylation of several regulatory kinases and lacks cross resistance to other standard chemotherapy agents. This is a first-in-man Phase I dose escalation study to determine the dose limiting toxicities, recommended Phase II dose, and pharmacokinetic (PK) profile, and to document any antitumor activity of ON-01910.Na. Methods: Patients had histologically confirmed solid tumors refractory to standard therapy. ON-1910.Na, formulated as a solution in PEG400, was administered as a 2-hour infusion on days 1, 4, 8, 11, 15, and 18 followed by a 10 day observation period for a total of 28 days per cycle. The initial dose was 80 mg and was escalated using an accelerated titration schedule; one patient was treated per cohort until grade 2 toxicity was documented. A dose confirmation cohort of up to 12 patients will be treated at the maximun tolerated dose (MTD). A comprehensive PK study was performed on days 1 and 15 of the first cycle, plus trough samples were collected. Results: Thirteen patients (7F, 6M; ages 46–73) have received 20 cycles. Dose levels of 80, 160, 320, 480, 800, 1280, 2080, and 3120 mg were evaluated in 8 patients, and a further dose of 4370 mg has been evaluated in 5 patients. Toxicities have been anemia (2 G1, 1 G2), leucopenia (1 G1, 1 G2), hyperglycemia (2 G1), elevated AST/ALT (1 G1, 1 G2), nausea (3 G1), diarrhea (3 G1), skeletal pain (5 G1, 1 G2), abdominal pain (2 G1), tumor pain (1 G2), and fatigue (3 G1, 1 G2), and have clustered at the latter 3 dose levels. PK analysis shows increasing ON-1910.Na exposure with increasing doses. ON-1910.Na has a low clearance (13 L/h), long half-life (20 h), distribution in excess of blood volume (58 L) and PK parameters are similar on days 1 and 15. Approximately 3-fold and 5-fold inter-subject variation in ON-1910.Na clearance was observed on days 1 and 15, respectively. No antitumor activity has been documented by standard criteria. Conclusions: Dose escalation is continuing. [Table: see text]