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PubMed2004

Contrast-enhanced MR Angiography of the renal arteries: blinded multicenter crossover comparison of gadobenate dimeglumine and gadopentetate dimeglumine.

PURPOSE: To prospectively and intraindividually compare 0.1 mmol/kg gadobenate dimeglumine with 0.2 mmol/kg gadopentetate dimeglumine for contrast material-enhanced magnetic resonance (MR) angiography of the renal arteries. MATERIALS AND METHODS: Institutional review board approval was granted by each of three participating centers. The study accorded with international standards for good clinical practice and Declaration of Helsinki and subsequent amendments. Patients gave written informed consent before enrollment. Patients (n = 34) underwent two MR angiographic examinations more than 48 hours but less than 12 days apart. Gadobenate dimeglumine followed by gadopentetate dimeglumine was administered in 18 patients; the order of administration was reversed in 16 patients. A 1.5-T MR imager was used with a phase-encoded three-dimensional spoiled breath-hold pulse sequence. Two blinded independent readers qualitatively assessed randomized subtracted maximum intensity projection images. A three-point scale for diagnostic quality (0, poor; 1a or 1p, moderate; and 2a or 2p, adequate [a and p refer, respectively, to absence and presence of vascular lesions]) was used to score each of nine segments of the abdominal aorta and both renal arteries (possible overall score, 18). Quantitative assessment (vessel signal-to-noise ratio [SNR], vessel-muscle contrast-to-noise ratio [CNR]) of source images was performed for regions of interest in supra-, juxta-, and infrarenal aorta segments and psoas muscle. Data were tested with analysis of variance for two-period crossover design. Interreader agreement was evaluated with Cohen kappa statistics. RESULTS: No difference in mean image quality between the two contrast agents was observed; scores for gadobenate dimeglumine and gadopentetate dimeglumine were 15.15 and 15.23 for reader 1 and 16.77 and 17.01 for reader 2. The order of contrast material administration likewise produced no quality differences: readers 1 and 2 reported scores of 14.4 +/- 4.2 (standard deviation) and 16.7 +/- 2.3, respectively, when gadobenate dimeglumine was given first, and 15.2 +/- 1.8 and 16.6 +/- 1.6, respectively, when gadopentetate dimeglumine was given first. Results of quantitative evaluation showed increasing SNR and CNR with gadobenate dimeglumine in segments at progressively lower levels of the aorta, but increases in SNR and CNR at the infrarenal aorta (48.3 vs 40.6 and 44.2 vs 36.4, respectively) were not significant (P = .05 for both). CONCLUSION: Gadobenate dimeglumine at a dose of 0.1 mmol/kg is comparable to gadopentetate dimeglumine at 0.2 mmol/kg for contrast-enhanced renal MR angiography.

Adult↗
PubMed2006

Leaching potential of heavy metals (Cd, Ni, Pb, Cu and Zn) from acidic sandy soil amended with dolomite phosphate rock (DPR) fertilizers.

There is an increasing concern on heavy metal leaching from the soils amended with sewage sludge. A column study was conducted to examine the extent of leaching of five important heavy metals (Cd, Ni, Pb, Cu and Zn) from an acidic sandy soil amended with different dolomite phosphate rock (DPR) fertilizers (an application rate of 1% fertilizers) developed from DPR and N-Viro (consisting of biosolids and fly ash) at 0%, 10%, 20%, 30%, 40%, 50% and 100% DPR. Ten leaching events were carried out with each event done at an interval of 7 days and with total leaching volume of 1183mm, which is equivalent to the mean annual rainfall of this region during the period of 2001-2003. Leachate was collected after each leaching event and analyzed for heavy metals. The maximum leachate concentrations of Cd, Ni, Pb, Cu and Zn were all below drinking water quality guidance limits set by Florida Department of Environmental Protection and World Health Organization, suggesting that the application of DPR fertilizers may not pose a threat to water quality by leaching. Most of leachate concentrations of Cd, Ni and Pb were below their detection limits and there were no significant differences between the control and the treatments with different DPR fertilizers. By contrast, there were higher leachate concentrations of Cu and Zn (ranging from 0.7 to 37.1mug Cu/l and 5.1 to 205.6mug Zn/l for all treatments) due to their higher contents in both the soil and different DPR fertilizers compared with Cd, Ni and Pb. The leachate concentrations of Cu and Zn for each treatment decreased with increasing leaching events. The differences in leachate concentrations of Cu and Zn between the control and the treatments with different DPR fertilizers containing N-Viro were significant, especially in the first several leaching events and, moreover, they increased with increasing proportion of N-Viro in the DPR fertilizers. There were similar trends in total losses of Cu and Zn after ten leaching events. Greater differences in both leachate concentrations and total losses of Zn between the control and the treatments containing N-Viro were noted. Total losses of Zn for the treatments containing N-Viro were 3.0-5.1 times higher than those for the control compared with 1.4-2.2 times higher for total losses of Cu, suggesting that greater proportions of Zn losses came from the DPR fertilizers due to the greater mobility of Zn in the DPR fertilizers compared with Cu.

Fertilizers↗
PubMed1985

A seven-year experience with donor-specific blood transfusions. Results and considerations for maximum efficacy.

Two hundred thirty-nine transplants have been performed following donor-specific blood transfusions (DSTs) since 1978. Graft and patient survival in 1- and 0-haplotype-matched transplants with DST pretreatment is comparable to HLA-identical results through 4 years. Graft survival in 174 consecutive nondiabetic, non-HLA-identical DST recipients shows that the transfusion effect persists for at least 4 years, with graft survival of 88 +/- 3% at that time, compared with 83 +/- 4% in the concurrent HLA-identical group. Graft function, as determined by serum creatinine, was the same in both groups. Graft and patient survival in 20 0-haplotype matched pairs with DST pretreatment is 100% at 2 years. Low-dose Imuran coverage during DST administration (n = 91) was compared with a concurrent group with no Imuran (n = 93). Imuran had its maximum effect in patients undergoing their first transplant and with a pre-DST PRA less than 10% (12% vs. 21% sensitization rate in the no-Imuran group). Imuran did not appear to confer any beneficial effect in primary transplants with high PRAs and in patients undergoing a second or third transplant. The majority of patients formally excluded from transplantation because of a post-DST positive B-warm crossmatch can now be successfully transplanted with the use of flow cytometry analysis to rule out previously undetectable low levels of anti-T-lymphocyte antibodies. Of 62 patients with a positive B-warm crossmatch alone since 1982, 73% had a subsequent negative fluorescence-activated cell sorter (FACS) crossmatch permitting transplantation. Preliminary results of a DST and cyclosporine treatment study are described. In conclusion, a long-term immunologic effect of DST has been confirmed and the indications and considerations for optimum use of the DST protocol have been more clearly defined.

Adolescent↗
PubMed2000

Cigarette smoking is associated with augmented progression of renal insufficiency in severe essential hypertension.

Hypertension-associated renal disease is a major cause of end-stage renal disease (ESRD) in the United States, but its risk factors remain incompletely defined. Identification and correction of amendable ESRD risk factors among patients with essential hypertension could reduce ESRD prevalence. Patients referred by their primary care physician for hypertension management to an academic nephrology clinic during calendar year 1995 were followed up prospectively. Studied patients had no evidence of secondary hypertension, diabetes, or primary renal disease. All were treated pharmacologically toward a target mean blood pressure (MBP) of 100 mm Hg or less. The course of renal function during follow-up was assessed as the slope of the reciprocal of plasma creatinine concentration (1/P(cr)) plotted against months of follow-up and as the change in calculated glomerular filtration rate (GFR) in milliliters per minute per month. The following patient characteristics were prospectively examined as possible predictive factors for altered renal function: age, sex, ethnicity, initial MBP, initial P(cr) level, initial level of urine protein excretion, and smoking status. Fifty-three patients were enrolled, and follow-up data were available for 51 patients after a mean follow-up of 35.5 months. Despite MBP reduction from 126.8 +/- 1.3 to 96.5 +/- 1.1 mm Hg (P < 0.0001), P(cr) level increased from 1.5 +/- 0.1 to 1.9 +/- 0. 2 mg/dL (P < 0.01). Multivariate regression analysis showed that smoking, greater initial P(cr) level, and black ethnicity were the only examined parameters that independently predicted both a decrease in the 1/P(cr) slope and calculated GFR with at least 95% confidence. Smoking was by far the most powerful of the examined factors, with initial P(cr) and ethnicity being much less predictive. These studies show for the first time that smoking is an independent risk factor for renal function decline in patients with severe essential hypertension.

Creatinine↗
PubMed1994

[A history of a hundred years of pharmaceutical education in Japan].

The history of a hundred years of pharmaceutical education in Japan is divided into six periods for the purposes of discussion. 1. Founding period of the pharmaceutical education in the Meiji era (1873-1879) The Department of Manufacturing Pharmacy, Faculty of Medicine, University of Tokyo was established in 1873 (now, Faculty of Pharmaceutical Sciences, the University of Tokyo). The purpose of this school was for professional training to accommodate growing imported Western drugs. 2. Building period of the pharmaceutical education in the Meiji era. (1880-1911) The Pharmaceutical society of Japan (academic) was established in 1880, and then 13 years later (1893) the Japan Pharmaceutical Association (professional) was established. The order of establishments, first academic and then professional, was opposite of the history in European countries. Twenty-nine schools of pharmacy were built in the Meiji era, however 20 schools of pharmacy have been closed. 3. Developing period the pharmaceutical education in the Taisho era and half of the Showa era (1912-1944) Seventeen pharmaceutical colleges were built in these periods. Pharmaceutical chemistry, pharmacognosy, hygenic chemistry, and manufacturing chemistry were mainly taught in these schools of pharmacy, however pharmacology, bacteriology, and biochemistry were not taught in these schools. 4. Reform of pharmaceutical education system after the World War II (1945-1960) In 1949, the Japanese education system was reformed, and then 46 colleges and universities of pharmacy were built. Then, the number of students doubled to 8,000. Graduates from pharmaceutical colleges and universities, pharmaceutical departments were eligible to take the national pharmacists licence examination which was conducted by the Ministry of Health and Welfare. The standard of the pharmaceutical education system was revised in 1656, recommending that the single pharmaceutical departments at the colleges of pharmacy by replaced by three departments, pharmacy, manufacturing pharmacy and biological pharmacy. 5. Improvement and developement of pharmaceutical education (1961-1985) Many universities and colleges were founded, and there are currently 46 universities and colleges. Every year, some 8,000 people who study pharmacy at 14 national, 3 public and 29 private universities enter the profession on graduation. About 60 percent found jobs in the pharmaceutical industry, and the remainder work as pharmacists in hospitals and pharmacies. 6. Recent movements toward reform in pharmaceutical education (1986-present) Two amendments to the Medical Services Law in 1986 and 1992 have specified clearly the role to be played by pharmacists and pharmacies within their local medical service and has sharpened the distinction between medicine and pharmacy. Thus, in 1994, the period required for graduation is proposed by a committee of the Ministry of Health and Welfare, supplementing of the current 4-year undergraduate pharmacy course with a 2-year postgraduate master's degree course or a 6-year new pharmaceutical education system including practical training in a medical institution for a period of at least 6 months.

Education, Pharmacy↗
PubMed2006

21st century neontology and the comparative development of the vertebrate skull.

Classic neontology (comparative embryology and anatomy), through the application of the concept of homology, has demonstrated that the development of the gnathostome (jawed vertebrate) skull is characterized both by a fidelity to the gnathostome bauplan and the exquisite elaboration of final structural design. Just as homology is an old concept amended for modern purposes, so are many of the questions regarding the development of the skull. With due deference to Geoffroy-St. Hilaire, Cuvier, Owen, Lankester et al., we are still asking: How are bauplan fidelity and elaboration of design maintained, coordinated, and modified to generate the amazing diversity seen in cranial morphologies? What establishes and maintains pattern in the skull? Are there universal developmental mechanisms underlying gnathostome autapomorphic structural traits? Can we detect and identify the etiologies of heterotopic (change in the topology of a developmental event), heterochronic (change in the timing of a developmental event), and heterofacient (change in the active capacetence, or the elaboration of capacity, of a developmental event) changes in craniofacial development within and between taxa? To address whether jaws are all made in a like manner (and if not, then how not), one needs a starting point for the sake of comparison. To this end, we present here a "hinge and caps" model that places the articulation, and subsequently the polarity and modularity, of the upper and lower jaws in the context of cranial neural crest competence to respond to positionally located epithelial signals. This model expands on an evolving model of polarity within the mandibular arch and seeks to explain a developmental patterning system that apparently keeps gnathostome jaws in functional registration yet tractable to potential changes in functional demands over time. It relies upon a system for the establishment of positional information where pattern and placement of the "hinge" is driven by factors common to the junction of the maxillary and mandibular branches of the first arch and of the "caps" by the signals emanating from the distal-most first arch midline and the lamboidal junction (where the maxillary branch meets the frontonasal processes). In this particular model, the functional registration of jaws is achieved by the integration of "hinge" and "caps" signaling, with the "caps" sharing at some critical level a developmental history that potentiates their own coordination. We examine the evidential foundation for this model in mice, examine the robustness with which it can be applied to other taxa, and examine potential proximate sources of the signaling centers. Lastly, as developmental biologists have long held that the anterior-most mesendoderm (anterior archenteron roof or prechordal plate) is in some way integral to the normal formation of the head, including the cranial skeletal midlines, we review evidence that the seminal patterning influences on the early anterior ectoderm extend well beyond the neural plate and are just as important to establishing pattern within the cephalic ectoderm, in particular for the "caps" that will yield medial signaling centers known to coordinate jaw development.

Animals↗
PubMed2002

Japanese national SIDS project: 1998-2000 research for the improvement of infant mortality.

The aim of the present study is to see if by conducting research on sudden infant death syndrome (SIDS), one of major contributing factors to infant mortality in Japan, infant mortality can be reduced. Concrete approaches taken in this study took four different directions: elucidation of SIDS etiology, prevention, elucidation of its social aspects (education) and the investigation of administrative aspects. At the same time, an attempt was made to get better grasp on the epidemiological trends in infant mortality, including that of SIDS. The idea behind this etiological approach was to unify hitherto separate approaches taken by those in epidemiological, physiological and pathological fields. A molecular-biological approach was also added. Physiologically hypothesized causes of SIDS--apnea and arousal disorder--together with the epidemiologically presumed risk factor of sleeping position, were examined jointly from a pathological viewpoint. Research in the first 2 years of the grant found that hypoxia reflected by gliosis in the brain stem arousal pathway was related to the duration of sleep apnea. Research in the final year of the grant found the possibility of organic fragility in the brain stem arousal pathway, particularly in periaqueducal gray matter and pedunculopontine nucleus reflected by apoptosis and neuronal plasticity. These findings gave support to the arousal disorder hypothesis in SIDS. Application of the restriction landmark genomic scanning (RLGS) method supported the possibility of locating a site for a SIDS-specific gene. The US collaborative home infant monitoring evaluation (CHIME) currently in use was evaluated. In addition, three new monitoring methods were developed: a non-invasive multi-channel pressure-sensing bed, microwave radar, and a pacifier that functions as a suckometer which can be used to evaluate a neonate's autonomic nervous functions. Social (educational) activities included: surveys of the current state of educational campaigns on SIDS in other countries, epidemiological evaluation of campaigns run by the Japan SIDS families' Association to evaluate the effectiveness of the SIDS campaign, and creation of a home page, mostly to inform the public about the output from this research group. "Guidelines for Death Scene Investigation of Sudden, Unexplained Infant Deaths: Recommendations of Interagency Panel on Sudden Infant Death Syndrome" was translated into japanese. Activities that concerned administrative measures included clarification of the unique nature of SIDS-related trials in Japan when compared to those in the United States. Other concrete administrative proposals were: a pressing need to increase the rate of SIDS-related autopsies to facilitate a better etiological understanding and, for this purpose, establishing regulations in local jurisdictions and amending Article 8 of the Postmortem Examination and Corpse Preservation Act, keeping in perspective the medico-economic evaluation of the japanese medical examiner system. For these proposals to be realized, establishment of a new office in charge of administrative and approved autopsies at the national level of government is desirable. Also pointed out were the different opinions held among specialists concerning the diagnosis of SIDS and their need to hold multiple conferences to unify their views. Basic data for these conferences were provided from epidemiological examinations of infant mortality.

Health Services Research↗
PubMed2005

[Legal involvement in psychiatric care].

In an amendment to the law regarding the treatment of the Mental Health patient in 1991, authority was given to the regional psychiatrists' committee to oversee compulsory orders for psychiatric hospitalization and compulsory orders for outpatient psychiatric treatment--and the extension of these orders. On 1st of June 2002 a pilot study was started in the Jerusalem region, in which mental health patients were to be represented by lawyers employed by the Ministry of Justice. The pilot study began as an initiative of the Ministry of Justice, in agreement with the Ministry of Health. We describe 3 cases which demonstrate that the procedure of legal representation lacks the necessary balance between medical and legal considerations. The decision of the regional psychiatrists' committee or the court is liable to worsen the patients' mental health status and even to accelerate aggression towards self or others. In rare cases a premature discharge based on legal considerations rather than medical evaluation may result in suicide, as demonstrated in one of the vignettes. The article discusses the unbalanced approach of legal versus medical consideration, preference of "liberty" over health and the "wish" of the patient rather than his well-being. The article considers the unbalanced approach of the legal system to appeals of therapists against the decision of the regional psychiatrists' committee, where prosecutors of the state decided an appeal of this kind over the staff treating the patient has no precedence. That was presented as justification that it should be rejected. A pilot study compared between patients discharged from compulsory hospitalization through regional psychiatrists' committee or court and patients discharged on a medical basis without legal interference. The study showed a shorter stay in the community in the first group (42%) compared to 75% stay in the community in the second group, after six months. We are of the opinion that the current provision of legal assistance is lacking the necessary balance between medical and legal considerations; the 'wish for freedom' as a default, although illogical, is within the new system of legal aid, and is more considerate and important than the 'best interests' of the patient and his health.

Hospitalization↗
PubMed1983

Intracoronary nifedipine in human beings: magnitude and time course of changes in left ventricular contraction/relaxation and coronary sinus blood flow.

Eight patients, all men, having at least 75% stenosis of the proximal, middle or both segments of the left anterior descending coronary artery, underwent intracoronary drug studies at the time of cardiac catheterization after saphenous vein bypass grafting. Nifedipine, 0.1 mg dissolved in saline solution, was infused into a left anterior descending graft that was the primary blood supply to each patient's anterior left ventricular wall and septum. High fidelity left ventricular pressure and its first derivative, dP/dt, and aortic pressure were sampled synchronously with coronary sinus blood flow by the thermodilution technique. The time constant of isovolumic pressure decay (T) was derived. In five patients, percent systolic shortening and mean shortening velocity were determined from myocardial markers implanted into the midwall of the myocardium at the time of cardiac surgery. In response to nifedipine, left ventricular systolic pressure decreased and end-diastolic pressure increased up to 60 seconds. Both positive and negative dP/dt also decreased up to 60 seconds, whereas coronary sinus blood flow increased up to 5 minutes. T was increased at 1 minute but returned to baseline by 3 minutes. Percent systolic shortening and mean shortening velocity were decreased at 1 minute but returned to control level by 3 minutes. Thus, although both left ventricular systolic and diastolic function were depressed by intracoronary administration of nifedipine, coronary sinus blood flow was augmented and remained increased long after changes in left ventricular contraction and relaxation had subsided. These temporal differences are consistent with animal studies showing a differential depressant effect of nifedipine on calcium uptake in smooth muscle and cardiac muscle.

Adult↗
PubMedDate not supplied

The ratification of the Convention on Psychotropic Substances 1971 and its transposition into national legislation in the Federal Republic of Germany.

The Single Convention on Narcotic Drugs, 1961, as amended by the 1972 Protocol Amending the Single Convention on Narcotic Drugs, 1961, and the Convention on Psychotropic Substances 1971 have been implemented in the Federal Republic of Germany as follows: (a) No distinction is made between narcotic drugs and psychotropic substances; all substances which are controlled and non-exempted preparations containing such substances fall under the legal designation of "narcotic drugs"; (b) The same control measures as for narcotic drugs apply to all substances in Schedules II, III and IV of the 1971 Convention, i.e. control of manufacture, trade, import and distribution; (c) Under the new Narcotics Act of the Federal Republic of Germany, which entered into force on 1 January 1982, preparations containing substances listed in Schedules II and III of the 1971 Convention are subject to the same full control measures, including mandatory special prescriptions, with the exception of approximately 50 preparations from substances in Schedule III of the 1971 Convention. These 50 preparations are also subject to import, export and transit controls under the Narcotics Act; (d) The approximately 50 preparations containing substances in Schedule III of the 1971 Convention, as well as all preparations containing substances in Schedule IV of this Convention (about 340), are treated as "exempted preparations" under the Narcotics Act. These preparations, however, may only be dispensed under medical prescription which is in conformity with the provisions of article 9, paragraphs 1 and 2 of the 1971 Convention; (e) Within the meaning of the Narcotics Act, the term "exempted preparations" denotes that no mandatory special prescriptions are required for these preparations but only the normal medical prescriptions. A number of regulations of the Narcotics Act apply to these exempted preparations, including: (i) Licence of manufacture; (ii) Records of dispensing of exempted preparations by the manufacturer to the first acquirer; (iii) Import, export and transit regulations for the exempted preparations containing substances listed in Schedule III (Schedule III B in the Narcotics Act); (iv) Export bans for countries which have prohibited import.

Drug Prescriptions↗
PubMedDate not supplied

Malignancies in the acquired immunodeficiency syndrome.

Aside from opportunistic infections, several neoplasms have been identified as part of the spectrum of acquired immunodeficiency syndrome (AIDS) as defined by the Centers for Disease Control. Kaposi's sarcoma (KS) was the first such neoplasm to be recognized within the spectrum of AIDS. Although the classic form of Kaposi's sarcoma had been well recognized prior to the epidemic of AIDS, it was quite distinct from the illness that was seen in its "epidemic" form in young homosexual males. In this setting, Kaposi's sarcoma is an aggressive disease, with extensive involvement of skin and mucous membranes, early dissemination to lymph nodes, impressive development of extreme lymphedema, even in the absence of bulky adenopathy, and rapid spread to visceral organs, including lungs and gastrointestinal tract, among others. Although rapid clinical progression and short median survival have been the rule, a spectrum of disease has been seen such that some patients have survived for many years with disease limited to the skin. Certain clinical and laboratory features, such as presence of unexplained fever, night sweats, weight loss ("B" symptoms), or significant T-4-lymphocytopenia, have been identified as indicators of poor prognosis. Various therapeutic interventions have been employed in epidemic KS, and although partial and complete remissions have occurred, no regimen yet reported has significantly improved the survival of treated patients. High-dose recombinant alpha interferon has produced response rates in approximately 30% of treated patients, although toxicity has been observed in approximately 30% as well. Likewise, vinblastine has produced similar response rates with no evidence of long-term efficacy or "cure." Aside from Kaposi's sarcoma, lymphoma primary to the central nervous system was recognized early in the AIDS epidemic as a criterion for inclusion within AIDS in patients less than sixty years of age. Several years after the initial reports of disease, it became apparent that specific types of systemic lymphoma were also quite extraordinary, and the definition of AIDS was amended in June 1985 to include high-grade B-cell lymphomas in individuals who had positive serology or virology for the human immunodeficiency virus (HIV). The AIDS-related lymphomas are characteristic, both pathologically and clinically. The vast majority of these cases have been high-grade B-lymphoid tumors of either immunoblastic or small-non-cleaved type (also known as "undifferentiated," Burkitt, or Burkitt-like).(ABSTRACT TRUNCATED AT 400 WORDS)

Acquired Immunodeficiency Syndrome↗
PubMed1995

Long-term outcome in kidney transplant patients with hepatitis C (HCV) infection.

To assess the prevalence and long-term impact of HCV on kidney transplant recipients, we assayed 716 pre-transplant sera using a first-generation ELISA. The anti-HCV positive sera were confirmed by a 6-antigen radioimmunoassay (RIA). Patients were followed up for 5 years. Graft survival, function, evidence of chemical hepatitis (AST > 2x normal), patient mortality and cause of death were evaluated. The prevalence of anti-HCV antibody was 10.3%. In the 638 patients who were followed up for 5 years, there were no differences in graft function, graft survival, overall mortality, or death from sepsis or liver disease. Peak AST levels were significantly higher in anti-HCV positive patients compared to anti-HCV negative patients. At 5 years, the AST levels remained significantly higher in the anti-HCV positive group, however, this was only 6 U/1 > normal. Liver biopsies performed 3 to 7 years post-transplant in 80% of anti-HCV positive patients with chemical hepatitis showed 12% CAH, 50% mild hepatitis and 38% normal histology. Six (9.7%) patients seroconverted from anti-HCV positive to anti-HCV negative 2 to 5 years post-transplant. The presence of anti-HCV does not appear to alter long-term patient or graft survival, and histologic evidence of severe chronic liver disease was rare in anti-HCV positive patients with chemical hepatitis. From these results, the presence of anti-HCV antibody should not preclude kidney transplantation.

Adolescent↗
PubMed1996

Risk assessment of use of cracked eggs in Canada.

In 1992, Agriculture and Agri-Food Canada (AAFC) amended its Egg Regulations to restrict movement of Canada C eggs (cracks) to federally registered processed egg stations for pasteurization. This was questioned by egg producers and some provinces on economic grounds. It was also in conflict with long-standing practices of marketing eggs in some provinces to retail stores, bakeries, restaurants and institutions or at the farm gate. In order to determine how much of a risk these eggs were to human health, AAFC requested that the Health Protection Branch (HPB) of Health Canada (HC) conduct a risk assessment. On the basis of outbreak data, the main hazard in these eggs was identified as Salmonella. Salmonellae may occasionally be present on shell eggs even after washing, and any Salmonella reaching the membranes can be transferred to an egg mixture through breaking, and will rapidly grow under improper storage conditions. A Relative Risk analysis showed that cracked eggs are 3 to 93 times more likely than uncracked shell eggs to cause outbreaks. A probability of illness of 1 in 3800 was derived from the 40 million cracked eggs produced in Canada and not pasteurized and the probable 10,500 illnesses arising from these. This was for the general population, but this would be greater for those who consume many shell eggs or would do so in an unsafe manner, or are more likely to be infected (5% of consumers who eat raw or lightly cooked eggs daily, rural communities with more opportunities for obtaining cracked eggs, and those who are immunocompromised and in institutions). Even though it is not possible to precisely determine the risk of salmonellosis through cracked eggs, this assessment indicated that there was enough of a concern that a management strategy was needed. Eight options for managing the risk were considered and ranked for acceptability by both HC and AAFC. Ideally, all cracked eggs should be broken and pasteurized, but this is impractical in certain regions of the country, and other options, such as sales to food processors operating under Good Manufacturing Practices (GMP), and at the farm gate in marked cartons and under controlled conditions, were considered to be acceptable, whereas sales to institutions and bakeries were not. This is the first fromal food-related microbiological risk assessment that HC has completed. Although this is a Canadian problem, any country producing eggs has to recognise that despite any regulations controlling the use of cracked eggs, economics will dictate that some of these will be consumed as whole eggs or egg products, and a management plan is desirable to limit hazardous practices associated with these eggs.

Canada↗
PubMed1987

Deep-etch visualization of 27S clathrin: a tetrahedral tetramer.

It has recently been reported that 8S clathrin trimers or "triskelions" form larger 27S oligomers upon dialysis into low ionic strength buffers (Prasad, K., R. E. Lippoldt, H. Edelhoch, and M. S. Lewis, 1986, Biochemistry, 25:5214-5219). Here, deep-etch electron microscopy of the 27S species reveals that they are closed tetrahedra composed of four clathrin triskelions. This was determined by two approaches. First, standard quick-freezing and freeze-etching of unfixed 27S species suspended in 2 mM 2-(N-morpholino)ethane sulfonic acid (MES) buffer, pH 5.9, yielded unambiguous images of tetrahedra that measured 33 nm on each edge. Second, the technique of freeze-drying molecules on mica (Heuser, J. E., 1983, J. Mol. Biol., 169:155-195) was modified to overcome the low affinity of mica in 2 mM MES, by pretreating the mica with polylysine. Thereafter, 27S species adsorbed avidly to it and collapsed into characteristic configurations containing four globular domains, each linked to the others by three approximately 33-nm struts. The globular domains look like vertices of deep-etched clathrin triskelions and the links, numbering 12 in all, look like four sets of triskelion legs. New light scattering and equilibrium centrifugation data confirm that 27S polymer is four times as massive as one clathrin triskelion. We conclude that in conditions that do not favor the formation of standard clathrin cages, low affinity interactions lead to closed, symmetrical assemblies of four triskelions, each of which assumes a unique puckered, straight-legged configuration to create the edges of a tetrahedron. Tetrahedra are similar in construction to the cubic octomers of clathrin recently found in ammonium sulfate solutions (Sorger, P. K., R. A. Crowther, J. T. Finch, and B. M. F. Pearse, 1986, J. Cell Biol., 103:1213-1219) but are still smaller, involving only half as many clathrin triskelions.

Animals↗
PubMed2004

EGF gene polymorphism and the risk of incident primary melanoma.

Overexpression of the epidermal growth factor (EGF) pathway has been implicated in melanoma pathogenesis, and a recent case-control study identified a single nucleotide polymorphism (G to A) in the EGF gene where the G allele was associated with increased EGF expression and an increased risk of melanoma. To further evaluate this association, we conducted a case-control analysis from the Genes, Environment, and Melanoma study at the University of Michigan site using two different study designs. Incident cases of histopathologically confirmed first primary melanoma that were diagnosed between January 1, 2000 and December 31, 2000 from the University of Michigan Melanoma Clinic (n = 330) were compared with the following two different sources of nonmelanoma controls: spouse/friend controls (n = 84) and healthy volunteer controls from a case-control study of psoriasis (n = 148). Using a second analytic design, comparisons between multiple primary melanoma cases (n = 62) and single primary melanoma cases (n = 330) were also evaluated to estimate odds ratios (ORs). Genotyping for the single nucleotide substitution (G to A) at position 61 in the 5' untranslated region of the EGF gene was performed from genomic DNA, and epidemiological risk factors were assessed through a telephone interview. When EGF genotypes were compared between incident primary melanoma cases and the nonmelanoma controls, the risk associated with the homozygous G/G genotype was not statistically significantly associated with an increased risk for incident primary melanoma compared with the homozygous A/A genotype [OR, 1.09; 95% confidence interval (CI); 0.65-1.85]. No strong associations with EGF G/G genotype were observed in comparisons of multiple primary and single primary melanoma cases (OR, 0.66; 95% CI; 0.25-1.73). Case subjects with tumors >/=3.5 mm compared with those <3.5 mm were not significantly associated with the G/G genotype (OR, 0.54; 95% CI; 0.12-2.35). Our data do not support a significant association between melanoma and the EGF 61*G allele or the homozygous G/G genotype. The EGF polymorphism is not a reproducible risk factor for melanoma or thick melanoma in our data. The two analytic approaches used in the study provide evidence against a strong association between EGF 61*G and melanoma and demonstrate the potential utility of case-case designs for evaluating the role of single nucleotide polymorphisms and cancer. Additional independent studies will be required to elucidate relationships between genetic variation in the EGF gene and risk of melanoma.

Alleles↗
PubMed2003

Cannabis-based medicines--GW pharmaceuticals: high CBD, high THC, medicinal cannabis--GW pharmaceuticals, THC:CBD.

GW Pharmaceuticals is undertaking a major research programme in the UK to develop and market distinct cannabis-based prescription medicines [THC:CBD, High THC, High CBD] in a range of medical conditions. The cannabis for this programme is grown in a secret location in the UK. It is expected that the product will be marketed in the US in late 2003. GW's cannabis-based products include selected phytocannabinoids from cannabis plants, including D9 tetrahydrocannabinol (THC) and cannabidiol (CBD). The company is investigating their use in three delivery systems, including sublingual spray, sublingual tablet and inhaled (but not smoked) dosage forms. The technology is protected by patent applications. Four different formulations are currently being investigated, including High THC, THC:CBD (narrow ratio), THC:CBD (broad ratio) and High CBD. GW is also developing a specialist security technology that will be incorporated in all its drug delivery systems. This technology allows for the recording and remote monitoring of patient usage to prevent any potential abuse of its cannabis-based medicines. GW plans to enter into agreements with other companies following phase III development, to secure the best commercialisation terms for its cannabis-based medicines. In June 2003, GW announced that exclusive commercialisation rights for the drug in the UK had been licensed to Bayer AG. The drug will be marketed under the Sativex brand name. This agreement also provides Bayer with an option to expand their license to include the European Union and certain world markets. GW was granted a clinical trial exemption certificate by the Medicines Control Agency to conduct clinical studies with cannabis-based medicines in the UK. The exemption includes investigations in the relief of pain of neurological origin and defects of neurological function in the following indications: multiple sclerosis (MS), spinal cord injury, peripheral nerve injury, central nervous system damage, neuroinvasive cancer, dystonias, cerebral vascular accident and spina bifida, as well as for the relief of pain and inflammation in rheumatoid arthritis and also pain relief in brachial plexus injury. The UK Government stated that it would be willing to amend the Misuse of Drugs Act 1971 to permit the introduction of a cannabis-based medicine. GW stated in its 2002 Annual Report that it was currently conducting five phase III trials of its cannabis derivatives, including a double-blind, placebo-controlled trial with a sublingual spray containing High THC in more than 100 patients with cancer pain in the UK. Also included is a phase III trial of THC:CBD (narrow ratio) being conducted in patients with severe pain due to brachial plexus injury, as are two more phase III trials of THC:CBD (narrow ratio) targeting spasticity and bladder dysfunction in multiple sclerosis patients. Another phase III trial of THC:CBD (narrow ratio) in patients with spinal cord injury is also being conducted. Results from the trials are expected during 2003. Three additional trials are also in the early stages of planning. These trials include a phase I trial of THC:CBD (broad ratio) in patients with inflammatory bowel disease, a phase I trial of High CBD in patients with psychotic disorders such as schizophrenia, and a preclinical trial of High CBD in various CNS disorders (including epilepsy, stroke and head injury). GW Pharmaceuticals submitted an application for approval of cannabis-based medicines to UK regulatory authorities in March 2003. Originally GW hoped to market cannabis-based prescription medicines by 2004, but is now planning for a launch in the UK towards the end of 2003. Several trials for GW's cannabis derivatives have also been completed, including four randomised, double-blind, placebo-controlled phase III clinical trials conducted in the UK. The trials were initiated by GW in April 2002, to investigate the use of a sublingual spray containing THC:CBD (narrow ratio) in the following medical conditions: pain in spinal cord injury, pain and sleep in MS and spinal cord injury, neuropathic pain in MS and general neuropathic pain (presented as allodynia). Results from these trials show that THC:CBD (narrow ratio) caused statistically significant reductions in neuropathic pain in patients with MS and other conditions. In addition, improvements in other MS symptoms were observed as well. Phase II studies of THC:CBD (narrow ratio) have also been completed in patients with MS, spinal cord injury, neuropathic pain and a small number of patients with peripheral neuropathy secondary to diabetes mellitus or AIDS. A phase II trial of THC:CBD (broad ratio) has also been completed in a small number of patients with rheumatoid arthritis, as has a trial of High CBD in patients with neurogenic symptoms. A phase II trial has also been evaluated with High THC in small numbers of patients for the treatment of perioperative pain. The phase II trials provided positive results and confirmed an excellent safety profile for cannabis-based medicines. GW Pharmaceuticals received an IND approval to commence phase II clinical trials in Canada in patients with chronic pain, multiple sclerosis and spinal cord injury in 2002. Following meetings with the US FDA, Drug Enforcement Agency (DEA), the Office for National Drug Control Policy, and National Institute for Drug Abuse, GW was granted an import license from the DEA and has imported its first cannabis extracts into the US. Preclinical research with these extracts in the US is ongoing.

Administration, Sublingual↗