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With a million, five-year federal grant, the School of Medicine establishes the Center for the Epigenetics of Common Human Disease, led by Andrew Feinberg, King Fahd Professor of Medicine. It is believed to be the first university-based research center devoted to studying epigenetics. Patrick Walsh mails 40, 000 free copies of a new DVD demonstrating his landmark methods for radical prostatectomy to surgeons worldwide. Funding for the 90-minute film is provided by a grateful patient. Jeffrey B. Palmer, an expert on swallowing disorders, is named director of the Department of Physical Medicine and Rehabilitation. The Robert Packard Center for ALS Research at Johns Hopkins receives a gift for research from students in the Long Island classes of science teacher David Deutch, whose amyotrophic lateral sclerosis, or Lou Gehrig's disease, was diagnosed at the center. For the 24th consecutive year, The Johns Hopkins University ranks first in the National Science Foundation's list of federally funded research and development expenditures.
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Which is his ; father marveled, and prayed that he would come unto him. Now when the angel came in, he saluted him, and said: Joy be with thee for evermore. And old Tobiah said: what joy can I have that sit here in darkness, and see not the light of heaven ? The young man said unto him: Be of good cheer, God shall help thee shortly. And Tobiah said unto him: Canest thou bring my son to Gabelius, unto the city of Rages in Medea ? And when thou comest again, I shall pay thee thy hire. And the Angel said unto him: I shall lead thy son, and bring him to thee again. Then Tobiah answered him: tell me I pray thee, of what house, or of what tribe art thou ? The angel Raphael said unto him: Asketh thou after the kindred of an hireling, or seekest thou a guide for thy son to go with him? But that I make thee not careful, I Azarias the son of great Hananias. And Tobiah answered: thou art come of a great kindred: but I pray thee, be not displeased, that I desired to know thy kindred. The Angel said unto him: thy son shall I lead forth safely, and bring him whole to thee again. Then answered Tobiah, and said: well, go on your way, and God be in your journey, and his Angel bear you company. So when they had prepared all things, that they would take with them in their journey: Tobiah bid his father and his mother fare well, and they went on their way both together. Now when they were gone, his mother began to weep, and said: The staff of our age thou hast taken away, and sent him from us. Would God that money had never been, for the which thou hast sent him away. If we had been content with our poverty, this had been great riches to us, that we saw our son her. Then said Tobiah unto her: weep not, our son shall come to us again safe and sound, and thine eyes shall see him. For I trust, that the good Angel of God shall bear him company, and order well all the things that he doth: so that he shall come to us again with joy. At these words his mother left from weeping, and held her tongue. [Chpt 6] So Tobiah went on his way, and a dog followed him, and the first night they abode by the water of the Tigris. Then went he out to wash his feet, and behold, there came forth an horrible fish to devour him. Of whom Tobiah was afraid, and cried with a loud voice, saying: Lord, he cometh upon me. And the Angel said unto him: Take him by the cheek blade, and draw him to thee. And he did so, and drew him upon the land. And the fish began to leap at his feet. Then said the Angel unto him: Take out the bowels of this fish, and as for the heart, the gall and the liver, keep them by thee. For these things are.
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POH reports 476 million shares outstanding, the most in the group. We believe the company will consider a stock split as the business matures. Only 57 companies in the sort have Wall Street analyst coverage. We believe our ongoing analyst research coverage will introduce excitement and investor interest of POH within the investment community. Average institutional ownership is 27%. Only 7% of POH shares are held by institutions. We expect institutional ownership to increase as the company builds on its revenue producing opportunities. Group share prices indicate a -41% decrease from their 52-week high prices. POH share price is off -30%, less than the No company in our group' average. sample traded at their 52 week high. These statistics point to a very difficult small cap biotech drug market. We did not value POH's science compared with the industry group. However, it is our belief that the company's science would probably be in the upper 25% of the group. Thus POH should be accorded a premium in share price to the group's average. On a comparative basis, POH common shares are significantly undervalued. As company sales increase, so should share prices rise in relation to the group. It is apparent that the investment community does not understand the mispriced values we have identified in our sort. Hence, this subset of the biotech drug related industry is not recognized nor understood by the investment community, and is by definition, an inefficient market.
Immune Responses Induced by Intranasal Immunization with Influenza H3N2-anti-H3N2 complex in Mice X. Yao, Y. Wen Fudan University, Shanghai, CHINA. Flagellin is an Effective Mucosal Adjuvant in the Development of a Protective Immune Response Against Yersinia pestis A. N. Honko, S. B. Mizel Microbiology and Immunology, Wake Forest University School of Medicine, Winston-Salem, NC. Induction of Active Immune Suppression by Co-immunization of DNA-protein Vaccines B. Wang, H. Jin, Y. Kang State Key Lab for Agro-Biotechnology, China Agricultural University, Beijing, CHINA. Aluminum Phosphate is an Active Adjuvant for CRM197 Pneumococcal Conjugate Vaccine PnC ; in Infants S. Lockhart1, W. Watson1, P. Fletcher2, A. Leeper3, S. Edwards4, M. McCaughey5, A. Dunning1, D. Sikkema1, G. Siber1 1Wyeth Research, Pearl River, NY, 2Woolwell Surgery, Plymouth, UNITED KINGDOM, 3Grove Surgery, Thetford, UNITED KINGDOM, 4North Cardiff Medical Centre, Cardiff, UNITED KINGDOM, 5Health Centre, Randalstown, UNITED KINGDOM. PyNTTTTGT Oligonucleotide IMT504 is a Potent Vaccine Adjuvant A. D. Montaner1, F. Elias2, J. M. Rodriguez2, J. Flo2, R. Lopez2, J. Zorzopulos1 1Instituto de Investigaciones Biomdicas, Fundacin Pablo Cassar., Buenos Aires, ARGENTINA, 2Immunotech S.A., Buenos Aires, ARGENTINA.
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Clinical evidence The Pharmacovigilance Working Party PhVWP ; of the CPMP initially considered the issue of withdrawal reactions and possible dependence associated with SSRIs and related antidepressants at the request of the United Kingdom. The PhVWP endorsed the conclusions of the United Kingdom assessment report of April 1998, that: The review had not identified evidence that SSRIs were drugs of dependence. The product information for all SSRIs should contain appropriate warnings about the wellrecognised withdrawal reactions. Formal clinical studies to evaluate the nature and extent of withdrawal reactions have not been carried out for all SSRIs.
A 13-year-old boy was referred to our hospital due to decreased visual acuity in both eyes over 2 years. He had no and chlordiazepoxide.
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0 A. Signs and Symptoms 1. Mild: Drowsiness, stupor, blurred vision. excessive dryness of mouth. 2. Severe: Respiratory depression, hypotension, coma, convulsions, cardiac arrhythmias and tachycardias. Also: urinary retention bladder atony ; , decreased gastrointestinal motility paralytic ileus ; , hyperthermia or hypothermia ; , hypertension, dilated pupils, hyperactive reflexes. B. Management and Treatment 1. Mild: Observation and supportive therapy is all that is usually necessary 2. Severe: Medical management of severe SINEQUAN overdosage consists of aggressive supportive therapy If the patient is conscious, gastric lavage, with appropriate precautions to prevent pulmonary aspiration, should be performed even though SINEQUAN is rapidly absorbed. The use of activated charcoal has been recommended, as has been continuous gastric lavage with saline for 24 hours or more. An adequate airway should be established in comatose patients and assisted ventilation used if necessary EKG monitoring may be required for severia days, since relapse after apparent recovery has been reported. Arrhythmias should be treated with the appropriate antiarrhythmic agent. ft has been reported that many ofthe cardiovascular and CNS symptoms of tricyclic antidepressant poisoning in adults may be reversed by the slow intravenous administration of 1 mg to 3 mg of physostigmine salicylate. Because physostigmine e rapidly metabohzed, the dosage should be repeated as required. Convutsions may respond to standard anticonvulsant therapy, however, barbiturates may potentiate any respiratory depression. Dialysis and forced diuresis generally are not of value in the management of overdosage due to high tissue and protein binding of SINEQUAN. S1NEQUAN isavailable as capsules contain, ng doxepin HClequivalentto: 10mg, 75mg, and 1 mg doxepin: bOttles of 100, 1000, and unit-dose packages of 100 10 x 10's ; . 25 mg and 50 mg doxepin: bottles of 100, 1000, 5000, and unit-dose packages of 100 10 x 10' ; . 150 mg doxepin: bottles of 50. 500, and unit-dose packages of 100 10 x 10's ; . SINEQUAN Oral ConcenIrate is available in 120 ml bottles with an accompanying dropper calibrated at 5mg, 10 mg, 15 m, 20 mg and 25 mg. Each ml contains doxepin HCI equivalent to 10 mg doxepin. Just prior to adminiatration, SINEQUAN Oral concentrate should be diluted with approximatetyl2o ml of water, whole or skimmed milk, or orange, grapefruit, tomato, prune or pineapple juice. SINEQUAN Oral concentrate is not physically compatible with a number of carbonated beverages. For those patients requiring antidepressant therapy who are on methadone maintenance, SINEQUAN Oral concentrate and methadone syrup can be mixed together with Gatorade lemonade, orange juice, sugar water, Tangy or watei but not with grape luce. Preparation and storage of bulk dilutions is not recommended. Mo, . dsUsd &on lnfomiIon on rsqus.
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Informal comparisons of the TP responsiveness of various parameters indicated that BMD and serum GH were much less responsive to TP at mg kg than other parameters. To statistically confirm this observation, data for each parameter in the TP group given 1 mg kg were transformed to express the percentage of prevention of the ORX effect see ``Materials and Methods'' ; . This transformation enabled a formal statistical comparison of the responsiveness of the different parameters to TP at mg kg Figure 4 ; . The greatest responsiveness to TP at mg kg was displayed by cholesterol 109% prevention ; and seminal vesicle weight 98.2% prevention ; . BMD 31% prevention ; and serum GH 8.5% prevention ; had the lowest responsiveness and were the only parameters whose responsiveness to TP at mg kg significantly differed from the seminal vesicles and chlorpheniramine.
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Tissues and urine samples. Megalin-deficient mice were produced by gene targeting as described in Willnow et al. 44 ; . Sex-matched wild-type and heterozygous littermates were used as controls. Mice were kept on a normal diet 0.08 mg vitamin B12 kg food ; with free access to drinking water. Urine was collected during a 16-h period from mice aged 1016 wk. Collections were performed simultaneously from megalin-deficient and sex-matched wild-type littermates. Urine was kept on ice during the sampling period to minimize protein degradation. For determination of vitamin B12 concentration, the kidney cortices were removed from anesthetized mice and immediately frozen. For immunocytochemistry, mouse kidneys were fixed by perfusion of 4% paraformaldehyde in 0.1 M cacodylate buffer, pH 7.4, through the left ventricle of the heart. Newly weened male Wistar rats were kept on a normal 0.041 mg kg food; Altromin, Lage, Germany ; or low-vitaminB12 0.011 mg kg food; Altromin ; diet for 60 days. Vitamin B12-overloaded rats were fed a normal diet for 60 days and injected subcutaneously with cyanocobalamine 10 g day; SAD ; for 17 days before death. All rats were at the same age when killed. The left renal vessels were ligated, and the kidney was removed and frozen for analysis of vitamin B12. The liver, intestines, and right kidney were fixed by retrograde perfusion with 4% paraformaldehyde in 0.1 M cacodylate buffer, pH 7.4, through the abdominal aorta. Random urine specimens were collected from three male patients suffering from Dent's disease, as well as from three control subjects, and frozen until processed for immunoblotting. All patients had clinical and laboratory features of the disease and a serum creatinine level 200 mol l. Antibodies. A monoclonal anti-B12 antibody ascites; Sigma ; and a polyclonal sheep anti-B12 antibody Biogenesis ; were used to identify B12 by immunocytochemistry. The affinity of the monoclonal anti-B12 antibody for different cobalamin forms [cyanocobalamin Sigma ; , hydroxycobalamin Gea ; , methylcobalamin Sigma ; , 5 -deoxyadenosylcobalamin Sigma ; , and dicyanocobinamide Sigma ; ] was analyzed by their ability to displace 57Co-cyanocobalamin 0.39 MBq ml; Amersham ; from the monoclonal anti-B12. One hundred microliters of the anti-B12 antibody diluted 1: 000 with 0.1 M PBS and 0.1% human albumin ORHA 20 21; Aventis Behring ; were incubated with 100 l of each of the cobalamins 4121, 000 nM ; and 50 l of 57Co-cyanocobalamin. After 20 h of incubation at 4C, free and bound cobalamin were separated using hemoglobin Difco ; -coated charcoal Sigma ; . Bound 57Co-cyanocobalamin was counted in a Wallac 1480 gamma counter. The analyses showed that hydroxycobalamin, methylcobalamin, and cyanocobalamin were able to displace labeled cyanocobalamin from the monoclonal antibody, whereas 5 -deoxyadenosylcobalamin and dicyanocobinamide were unable to displace cyanocobalamin from the antibody Fig. 1 ; . Polyclonal anti-rabbit TC antibody was produced by immunization of a guinea pig by five consecutive injections totaling 0.5 mg of rabbit TC purified from rabbit serum 29 ; . Polyclonal anti-human TC was raised against recombinant human TC. For double-labeling experiments to identify lysosomal structures, we used polyclonal rabbit anti-rat LAMP-1 kindly provided by Dr. Ira Mellman ; or anti-rat cathepsin B Upstate Biotechnology ; . The following secondary antibodies were used: horseradish peroxidase HRP ; -conjugated rabbit anti-guinea pig, goat anti-rabbit, goat anti-mouse, or rabbit anti-sheep IgG DAKO ; , FITC-conjugated goat anti-mouse IgG DAKO ; , rhodamine-conjugated swine anti-rabbit IgG and chlorpromazine.
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By topical decongestants. According to the literature consulted, naloxone was employed for just one fifteenmonth old patient who had been exposed to oxymetazoline, without success. 9 Once an hour has passed after ingestion, gastric lavage is no longer recommendable due to the rapid rate of absorption and the central neural depressive effect , increasing aspiration risks.5, 7, 9, 22 An isolated dose of activated charcoal may be of use up to one hour after ingestion, but the risk of aspiration is still present.5, 7, 9, 23 Despite these risks, a single dose of activated charcoal N 21 ; and gastric lavage N 14 ; were used with symptomatic children and there is no record of aspiration in any of the patients. Treatment of the clinical manifestations is basically symptomatic and supportive, including mechanical ventilation for patients with severe respiratory depression, while the use of atropine is questionable, 5, 7, 9 but was used with one patient in this series. Remission of the symptoms generally occurs in 24 to hours.1, 5, 7, 9-14, In the current series, mechanical ventilation was employed in just one case and 68.4% of the patients were asymptomatic 24 hours after exposure. Although 32 cases were excluded, the data from this group suggest that their removal will not have interfered with the results presented by the study group, indicating that there should not have been selection bias. Within the methodological limits of a retrospective, it can be concluded that acute exposure to imidazoline derivatives, particularly to naphazoline and in children less than three years old, causes, in the majority of cases, irrespective of the exposure route oral or nasal ; , the rapid appearance of clinical manifestations of intoxication, of which neurological, cardiovascular and respiratory depression stand out. These manifestations abate, in general within 24 hours of exposure. It can also be inferred that products containing these active ingredients should be indicated with great caution for this age group, calling particular attention to the risks of administering Multigen-AL.
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CONCLUSION: There is a very high prevalence of moderate or severe LVDD in patients with suspected myocardial ischemia, especially if there is an abnormal SST or prior coronary revascularization. CLINICAL IMPLICATIONS: There is a very high prevalence of moderate or severe LVDD in patients with ischemic heart disease, especially in those with an abnormal LVEF. DISCLOSURE: Gautham Ravipati, None. ISOLATED AND SIGNIFICANT LEFT MAIN CORONARY ARTERY DISEASE: DEMOGRAPHICS, HEMODYNAMICS AND ANGIOGRAPHIC FEATURES Nitin Mahajan MD * Deepak Thekkoott MD Gerald Hollander MD Bilal Malik MD Sunil Abrol MD Jacob Shani MD Edgar Lichstein MD Maimonides Medical Center, Brooklyn, NY PURPOSE: This paper describes the demographic, angiographic and hemodynamic characteristics of forty-six patients with isolated and significant LMCA disease ILMCAD ; in an attempt to determine the etiology of ILMCAD. METHODS: We identified 46 patients with ILMCAD from our database over 10 years Group I ; and compared them with 83 consecutive patients that underwent catheterization in our lab Group II ; . We also compared ostial vs. distal ILMCAD. RESULTS: Group I represents 0.1% of catheterization patients. Unstable angina was the commonest presentation followed by non ST elevation myocardial infarction, elective catheterization, syncope and dyspnea on exertion. The comparison of study groups is shown in table 1 and figure 1.Mean left ventricular ejection fraction is similar in both sub-groups ostial disease-49%, distal disease-50% ; . About half the patients with ILMCA n 24 46: 52% ; disease had the classical "jet streaming" of contrast and was seen more commonly in patients with ostial and mid ILMCA disease. About one-fifths of ILMCA patients 9 46: 20% ; demonstrated retrograde filling from right coronary artery. Ventricularization was seen in only 4 patients. The majority of patients 23 44: 52% ; had normal segmental wall motion. An inverse relation was seen between the severity of LMCA stenosis and left ventricular ejection fraction. The left ventricular end diastolic pressure had no correlation with left ventricular ejection fraction or severity of LMCA stenosis and charcoal.
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SECTION 2 RESULTS AND CONCLUSIONS LIGHTER FLUID EMISSION ESTIMATES Volatile organic compounds are emitted when charcoal lighter fluid is used, but these emissions are difficult to quantify. Evaporative VOC losses occur from the lighter fluid, and combustion VOC losses occur from burning 1 ighter fluid-soaked charcoal briquettes. Limited tests have been performed to date, and none have attempted to distinguish the lighter fluid combustion emissions from the charcoal briquette combustion emissions. Three studies that attempted to estimate VOC emissions from charcoal lighter fluid use were reviewed in this study. The results of these studies are summarized here, and are discussed in more detail in Section 3. Table 1 presents a summary of the emissions information as found in studies by the U. S. Testing, an independent South Coast Air Quality Management District; '.? testing firm hired by the Clorox Company; 3 and the U. S. Environmental Protection Agency, Air and Energy Engineering Research Laboratory AEERL ; . The SCAQMD estimate is not based on actual testing, but is based instead on assumptions of the emission factor and evaporation rate for charcoal 1 ighter fluid. The Clorox Company's test examines only evaporation of lighter fluid prior to ignition. The test conducted by the EPA is the most complete o f those conducted to date in that evaporation and combustion emissions are monitored Appendix B ; . However, it is difficult to distinguish the charcoal combustion emissions from those of the lighter fluid. National emissions of VOC from lighter fluid use can best be estimated by combining the data provided by the Clorox Company and the EPA. The national estimate of 1, 110 tons.VOC yr 1, 000 Mg yr ; due to evaporation of charcoal lighter fluid lies in the mid range of the estimates reviewed, and is calculated from the evaporative data provided by the Clorox Company. Evaporation and combustion o f lighter fluid are estimated to yield a national total o f 14, 500 tons VOC yr 13, 150 Mg yr ; , based on the EPA's test. The SCAQMD recently conducted a more detailed eval uat i on of pol 1 utant emisslons from various methods of igniting charcoal briquettes.' The charcoal and chlorzoxazone.
The majority of the finds in the housepit are worked flint and potsherds. No bones had been preserved. In the culture layers we also found charcoal and 505 kg of fire-cracked stones. The following is based on a preliminary examination. In the house approximately 16, 9 kg of ceramics or 20991 potsherds were found. Only 7 % of the potsherds were ornamented, and 7 % were rim sherds. Most of the ornamented sherds were found in the upper layers, but ornamented sherds of the same types also occurred in the lower layers. Sherds ornamented with toothed-stamped decoration predominate Fig. 5, Table 1 ; . Often the toothed-stamped decoration was placed in several horizontal lines. Only three sherds were decorated with horizontal zones with short oblique, toothed-stamped lines. Potsherds with several horizontal grooves or lines are also very common. Cardium placed in horizontal lines occur but less frequently. Many sherds are ornamented with 1-3 horizontal lines of fingergrooves or cordons placed near the rim.
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Multidisciplinary process, and scientists trained in bioinformatics, chemistry, biochemistry, molecular biology, electrophysiology, genetics, immunology and histology will all be needed to play their roles. The pharmacologist, with a knowledge of the principles of drug action and the ability to think in an integrated way about what happens when a drug candidate is administered, is in a unique position to bring specialist knowledge together and make informed judgements on whether or not the new chemical entity has the potential to become a therapeutic agent. Thus, in vivo training and knowledge and appreciation of integrated responses must be given proper emphasis in any pharmacology courses that are offered now and for the foreseeable future. What has been said for in vivo pharmacology also applies to in vivo physiology. The Future of in vivo Pharmacology Regulatory bodies and governments worldwide are demanding more and more information on the safety, potential side-effects and pharmacokinetics of new therapeutic agents before they are tested in humans. The development of new drugs is becoming an increasingly costly exercise, particularly when Phase II and Phase III trials in patients are undertaken. Companies and institutions are not prepared to embark on a multi-million-pound development program unless there is reliable evidence from animal studies that what happens in a test tube or in isolated cells has therapeutic potential. The Human Genome Project will provide thousands of possible drug targets, but the rate-limiting step will be understanding the function and physiological importance of these new proteins. Proof of concept will become increasingly important as targets are selected, and whole-animal studies, including the development of transgenic animals, will play a crucial role. Further along the development program, the design of appropriate clinical studies to show efficacy and therapeutic benefit at an early stage will be a scientific process that is based on knowledge of dose-response relationships, maximum tolerated dose and pharmacokinetics in whole animals. The final outcome of the molecular biology revolution is not, therefore, a diminution of the importance of in vivo pharmacology, but a re-emphasis of its central role in drug discovery and improved therapeutics. The skills, techniques and principles of in vivo animal experimentation are essential to the discovery and development of new and improved drugs. We must ensure we capitalize on the Human Genome Project to make the necessary advances in medical understanding of the etiology and pathology of diseases, and to find ways of treating currently untreated conditions and resistant viruses and bacteria and cholestyramine.
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