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Biomedical subjects

A Hanson

Publications and source records attributed to A Hanson.

At least 19 recordsLinked to original sources

Radical cations of benzo[a]pyrene and 6-substituted derivatives: reaction with nucleophiles and DNA.

1. Oxidation of benzo[a]pyrene (BP) by I2 in the presence of AgClO4 in benzene generates the BP.+ClO4-.AgI complex. This same method was used to produce radical cations from 6-FBP, 6-ClBP, 6-BrBP and 6-CH3BP. 2. Reaction of the BP, 6-FBP, 6-ClBP and 6-BrBP radical cation perchlorates with H2O produced BP 1,6-, 3,6- and 6,12- dione, whereas 6-CH3BP.+ClO4-.AgI yielded 6-CH2OHBP. 3. When BP.+ClO4-.AgI and 6-FBP.+ClO4-.AgI were reacted with NaOAc in H2O/CH3CN (9:1), 6-OAcBP was formed, in addition to the quinones. In the case of 6-ClBP.+ClO4-.AgI, a small amount of 1-OAc-6-ClBP and 3-OAc-6-ClBP was formed in addition to the diones, whereas for 6-BrBP and 6-CH3BP the reaction products were BP diones and 6-CH2OHBP respectively. 4. These results confirm the localization of charge in the BP.+ at C-6, followed by C-1 and C-3. 5. The reaction of BP with NOBF4 in CH2Cl2 produced BP.+BF4-, radical cation free of complexation with inorganic salts. 6. Reaction of BP.+BF4- with DNA produced the depurinating adducts BP-6-C8Gua, BP-6-C8dGua and BP-6-N7Gua.

Animals

Microcalorimetric study on myocardial metabolism in a hibernator and two nonhibernators at 20 degrees C and 37 degrees C.

Metabolic activity in cardiac tissue slices from the guinea pig (GP), the rat (RT), the nonhibernating summer and winter hedgehog (SH and WH), respectively, was determined at 20 degrees and at 37 degrees C from their rates of heat production, P, (units, W/g tissue) by direct and indirect calorimetry. Energy-linked transport of Na+ and K+ in the tissues was determined from changes in metabolic rate induced by specific inhibition of the Na/K pump, the functional expression of Na/K-ATPase, the pacemaker enzyme in energy production assigned the role of transporting Na+ and K+ out of and into the cell. The results indicate a higher rate of energy production and utilization in the cardiac tissue of the hedgehog than in that of the nonhibernators, the rat and the guinea pig, at both temperatures. At 37 degrees C the rate at which the cardiac tissue from the hedgehog consumed oxygen was as much as six times that registered for the guinea pig. The temperature coefficients of P and of the Na/K pump in the tissues from the two groups of hedgehogs were significantly higher than in the tissues from the rat and the guinea-pig (P < 0.001). The determined metabolic indices, the basal rate of heat production P, the rate of oxygen consumption, P(O2) in thermal units (W/g tissue), and the Na/K-pump capacity (PC) indicate species-specific differences between the animals. Both PC and its variation with temperature, delta PC/delta T(o)C, were in the order WH > SH > RT > GP. These results indicate that the hedgehog's cardiac tissue, in comparison with that of the nonhibernators, has a greater capacity to generate energy in general and for active transport of Na+ and K+ at 37 degrees C after exposure to a lower temperature. A role is suggested for the Na/K-ATPase and some other unique rate-limiting enzymes in the metabolic pathway for the observed differences in temperature tolerance and cardiac performance between hibernators and nonhibernators.

Animals

Screening for psychiatric morbidity in a medical outpatient clinic for HIV infection: the need for a psychiatric presence.

OBJECTIVE: To ascertain the prevalence and type of psychiatric morbidity present in HIV infected patients presenting for the first time to a specialty HIV medical clinic. Also, to develop a way of screening for psychiatric cases in this setting using established self-report questionnaires. METHOD: Fifty patients who presented consecutively for medical care at the Johns Hopkins Hospital General HIV Clinic participated in this study. These patients were first screened using the General Health Questionnaire and the Beck Depression Inventory and subsequently underwent a comprehensive neuropsychiatric evaluation. RESULTS: Fifty-four percent were found to suffer from a psychiatric disorder with an additional 22 percent from an active substance use disorder. These rates are one-and-one-half to two times higher than those reported from other medical clinics. The GHQ and BDI used together as screens could identify psychiatric "cases" with a sensitivity of 81 percent and a specificity of 61 percent, an efficacy similar to that found in other clinics. CONCLUSIONS: Given the high prevalence of psychiatric disorders in HIV infected patients presenting for medical care, screening, evaluating, and treating for these disorders is crucial and should be pursued systematically. This is best done through the presence of a psychiatric team within HIV medical clinics rather than in affiliation with such clinics.

Ambulatory Care Facilities

Surface damage to cobalt-chrome femoral head prostheses.

Fifty-four cobalt-chrome alloy femoral heads were retrieved at revision surgery or at post-mortem; 23 came from uncemented, eight from hybrid and 23 from cemented hip arthroplasties. The uncemented and hybrid implants had porous coating, metal backing and modular femoral heads; with one exception none of the cemented implants had any of these. Twenty-five of the 31 heads from uncemented and hybrid arthroplasties, and 11 of the 23 heads from cemented arthroplasties showed surface damage involving more than 25% of the surface. Scanning electron microscopy revealed multidirectional fine scratches 1 micron to 10 microns in depth and width which appeared to have been made by fine, hard particles. There was a higher rate of such damage in the uncemented and hybrid arthroplasties than in the cemented implants, suggesting that the abrasive particles were mainly released from the metal, rather than from the cement or polyethylene components of the implants.

Adult

Antibodies to a recombinant glutamate-rich Plasmodium falciparum protein: evidence for protection of individuals living in a holoendemic area of Liberia.

A Plasmodium falciparum antigen gene coding for a 220-kD glutamate-rich protein (GLURP) has been cloned, and the 783 C-terminal amino acids of this protein (GLURP489-1271) have been expressed as a beta-galactosidase fusion protein in Escherichia coli. The encoded 783 amino acid residues contain two areas of repeated amino acid sequences. Antibodies against recombinant GLURP489-1271, as well as against a synthetic peptide corresponding to GLURP899-916, and against a synthetic peptide representing the major glutamate rich repeat sequence from the P. falciparum ring erythrocyte surface antigen (Pf155/RESA) (EENV)6 were examined in 423 individuals (age range 30 days-78 years) living in a malaria holoendemic area of Liberia. In the 5-9-year-old age group, subjects with anti-GLURP489-1271 antibody concentrations greater than the mean value of the group had lower parasite densities than those with low antibody concentrations (P = 0.0151). High levels of anti-GLURP899-916 antibodies did not correlate with low parasite densities. However, high levels of anti-(EENV)6 antibodies were associated with significantly lower parasite densities in the 2-4-year-old age group (P = 0.0189). There was no correlation between the anti-GLURP489-1271 and anti-(EENV)6 antibody responses. The data provide indirect evidence for a protective role of antibodies reacting with recombinant GLURP489-1271 as well as with the synthetic peptide (EENV)6 from the Pf155/RESA.

Adolescent

Effects of hemorrhagic shock and retransfusion on catalase and superoxide dismutase activities in rabbits.

The effects of hemorrhagic shock and retransfusion on the activities of two endogenous antioxidant enzymes, catalase and superoxide dismutase, were studied in male New Zealand white rabbits. Following instrumentation and stabilization, blood was withdrawn to reduce mean arterial pressure to 35 mmHg (SHOCK). After 60 min of shock, the warmed autologous blood was infused and the animals were allowed to recover for an additional 30 min (RETRANS). CONTROL animals were instrumented but not bled or transfused. A 60 min period of hemorrhagic shock had no significant effect on tissue or plasma activities of catalase or superoxide dismutase. However, transfusion following hemorrhagic shock resulted in an increase in catalase activity of nearly two-fold in the liver and five-fold in the small intestine. In contrast, superoxide dismutase activity remained unchanged after retransfusion in other tissues and in plasma. These results indicate that superoxide dismutase and catalase activities may be preserved or even induced following transfusion for hemorrhagic shock.

Animals

Simulated paraphilias: a preliminary study of patients who imitate or exaggerate paraphilic symptoms and behaviors.

In a consecutive series of admissions to the Johns Hopkins Sexual Disorders Unit, 4 out of 20 patients appeared to have simulated paraphilic symptoms that further assessment indicated were either exaggerated or not present. The paper presents case histories of these 4 patients. A descriptive comparison is made between these patients and control groups of patients who admitted having paraphilic symptoms and a group of patients accused of having paraphilic symptoms but who denied them. Patients who simulated paraphilias tended to be self-referred (75%) and without current legal charges (100%). None of these patients was referred or sought treatment for pedophilia, in contrast to the other two patient groups, in which pedophilia accounted for 75% of the referrals. Several possible explanations for why patients might simulate paraphilias and implications for therapists who evaluate or treat sex offenders are discussed.

Adult

Inhibition of complement components C3 and C4 by cadralazine and its active metabolite.

The effect of cadralazine and its active metabolite CGP 22639 on the covalent binding reaction of C4 and C3 has been studied. Trypsin-Sepharose was used to activate radio-labelled C3 and C4 and binding of the radio-labelled protein to the trypsin-Sepharose was measured. Cadralazine inhibited 50% of the binding of C3 and C4 at concentrations of 19 mmol/l and 15 mmol/l, respectively. Its active metabolite was more potent and inhibited 50% of the C3 and C4 binding at concentrations of 8 and 3.5 mmol/l, respectively. These concentrations are much higher than those found in plasma during therapy. This is consistent with the clinical observation that in patients with normal kidney function cadralazine is not an inducer of SLE.

Antihypertensive Agents

Isolation of a simian immunodeficiency virus related to human immunodeficiency virus type 2 from a west African pet sooty mangabey.

Two of 25 healthy pet sooty mangabey (SM) monkeys (Cercocebus atys) living in West Africa were seropositive by immunoblot when surveyed for antibody to simian immunodeficiency virus of macaques (SIVmac). SIVsmLIB1 was isolated from one of the pet sooty mangabeys. Nucleotide sequence data showed that this isolate is a member of the SIVsm/human immunodeficiecy virus type 2 (HIV-2)/SIVmac group of primate lentiviruses. Furthermore, sequence comparisons revealed extensive genetic diversity among SIVsm isolates similar to that observed previously in SIV isolates from naturally infected African green monkeys. These observations provide additional evidence for monkey-human cross-species transmission of SIVsm as the source of HIV-2 infection of human.

Animals

The value of ear lobe oximetry in the assessment of disability in asbestos-related disease.

Thirty-four asbestos workers, with either asbestosis, diffuse pleural thickening, calcified pleural plaques, or with comparable asbestos exposure but no evidence of asbestos-related disease and seven normal controls underwent a progressive exercise test. The subjects were categorized on the basis of lung function tests and PA chest X-rays. During the exercise test oxygen saturation was measured continuously by an ear lobe oximeter. The asbestosis and diffuse pleural thickening groups showed significant oxygen desaturation on exertion, confirming that both these conditions give rise to appreciable respiratory disability.

Asbestosis

Plasmodium falciparum-inhibitory monoclonal antibodies produced by human hybridomas.

Stable human hybridomas were generated that produced inhibitory anti-Plasmodium falciparum monoclonal antibodies. Peripheral blood lymphocytes, obtained from adults in Liberia, a malaria endemic area, were immortalized with Epstein-Barr virus and then fused with KR4, a human, lymphoblastoid cell line. Stable hybridomas that produced anti-P. falciparum monoclonal antibody were identified by an ELISA assay that used the trophozoite and schizont antigens of both the Honduras I and FCR3 parasite strains. Monoclonal antibodies produced by selected hybridomas derived from lymphocytes of two individuals were subsequently studied. The anti-parasite antibodies were produced at 1-3 micrograms/ml in culture supernatants. All of the monoclonal antibodies bound specifically to trophozoites and schizonts of both strains of parasite in an indirect immunofluorescence assay and inhibited production of ring stage parasites by more than 90% when added to trophozoite or schizont containing erythrocytes in culture. Western immunoblot analysis of antigens obtained from trophozoites and schizonts (parasite age span of 36 to 48 h) was performed using either affinity purified or ammonium sulfate-concentrated monoclonal antibody. Antibody from three hybridomas which bound primarily to antigens of the Honduras 1 strain had Mr of approximately 140,000, 130,000 and 123,000.

Animals

Metabolism of hydralazine in man. Part II: Investigation of features relevant to drug safety.

The metabolism of hydralazine (1-hydrazinophthalazine hydrochloride, Apresoline) was investigated in 17 hypertensive patients of known acetylator status who were chronically treated with oral doses of 50 mg b.i.d. or 100 mg b.i.d. hydralazine. The acetylator status was assessed either by the monoacetyldapsone/dapsone ratio or by the isoniazide plasma half-life. In each patient the tests were performed on two different days of treatment and they included the analyses of four hydralazine metabolites (NAc-HPZ, 3OH-MTP, MTP and TP), as well as apparent hydrazine in urine and also the determination of plasma concentrations of apparent hydralazine. All data of the two experiments performed within an interval of at least five days were in good agreement, thus indicating that the patients were in pharmacokinetic steady states. No correlation was detectable between any of the determined amounts of metabolites of hydralazine and the assigned acetylator status of the patients. On the other hand the rank order of the urinary yields of the two main metabolites NAc-HPZ and 3OH-MTP suggest to be a representative scale for the patients' status in respect to the biotransformation of the drug itself. The urinary yield of apparent hydrazine is dependent on the pH applied during the analyses and is not correlated with any of the other data recorded. The findings of the present study support the assumption that measuring a relevant prominent metabolite of the drug itself may lead to a more reliable assessment of the particular metabolic status of the patients than by classification through a non treatment related foreign compound.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylation

Monthly antimalarial chemotherapy to children in a holoendemic area of Liberia.

Two hundred and eighty-two children, two to nine years old, were included in a prospective three-year study in four villages with holoendemic malaria. In three villages the children received monthly doses of either chloroquine, pyrimethamine or chlorproguanil respectively for two years. In the fourth, vitamin tablets were used as placebo. Presumptive treatment with chloroquine (10 mg base kg-1) was given to all children with fever of suspected malarial origin. The two-year drug distribution was satisfactorily fulfilled to 168 children. Surveys, including physical and laboratory examinations were performed every six months, four weeks after medication. A fifth village was only visited at the start of the study and after two years. The mean crude parasite rate was initially 92%. Plasmodium falciparum was the main species. Splenomegaly was recorded in all children. In the chloroquine-treated children, the parasite rates varied between 30% and 50% during the study. By the end of the second year the spleen rate was reduced from 100% to 50%. Reported episodes of fever were reduced to half and mean haematocrit levels increased by 6% in comparison with children receiving the placebo. Total IgG concentrations were reduced from 36.7 g l-1 to 25.9 g l-1, whereas no significant decrease was observed in malarial seropositivity as measured by indirect immunofluorescence. Chlorproguanil had a weaker impact on parasitaemia with parasite rates between 50% and 90%. However, the spleen rate was reduced to 67% and there was a significant reduction of reported fever episodes. Mean haematocrits increased by 4%. Total IgG decreased from 31.8 g l-1 to 23.8 g l-1. In contrast, in the pyrimethamine group, the placebo group and the untreated group from the fifth village, the malariometric indices after two years were comparable to each other and to the initial values. During the third year only presumptive chloroquine treatment was given, and by the end of the study all malariometric indices were again comparable. From clinical observations there was no apparent impairment of protective immunity to malaria from the two years of regular distribution of the drugs. We conclude that a certain degree of malaria control could be achieved in Liberian children by the administration of monthly doses of chloroquine 10 mg base kg-1. The administration of chlorproguanil (1.5 mg kg-1) represents an alternative regimen.

Antimalarials

Cost comparison of unit dose and traditional drug distribution in a long-term-care facility.

Unit dose and traditional drug distribution systems were compared in a 352-bed long-term-care facility by analyzing nursing time, medication-error rate, medication costs, and waste. Time spent by nurses in preparing, administering, charting, and other tasks associated with medications was measured with a stop-watch on four different nursing units during six-week periods before and after the nursing home began using unit dose drug distribution. Medication-error rate before and after implementation of the unit dose system was determined by patient profile audits and medication inventories. Medication costs consisted of patient billing costs (acquisition cost plus fee) and cost of medications destroyed. The unit dose system required a projected 1507.2 hours less nursing time per year. Mean medication-error rates were 8.53% and 0.97% for the traditional and unit dose systems, respectively. Potential annual savings because of decreased medication waste with the unit dose system were $2238.72. The net increase in cost for the unit dose system was estimated at $615.05 per year, or approximately $1.75 per patient. The unit dose system appears safer and more time-efficient than the traditional system, although its costs are higher.

Costs and Cost Analysis

Plasma fibronectin levels in acute and recovering malnourished children.

58 malnourished children (mean age 18 months) with a clinical diagnosis of marasmus or kwashiorkor were studied with respect to plasma fibronectin levels, plasma total solids, spun hematocrits, heights, weights, mid-arm circumferences, and head circumferences. Bimodal distributions were demonstrated for plasma fibronectin versus weight deficits, total solids, hematocrits, and mid-arm circumference in children 12 months of age and older (p less than 0.003 for all). The mean plasma fibronectin level for controls was 253 micrograms/ml. The mean level for the malnourished group was 96 micrograms/ml (p less than 0.0001). Malnourished children with initial plasma fibronectin levels above 100 micrograms/ml had a higher survival rate than those with levels less than 100 (92 versus 69%). With successful therapy, plasma fibronectin levels rose quickly in most children often before detectable changes were noted in clinical and other laboratory parameters. An overshoot of the mean normal levels was observed with successful treatment wherein the mean levels rose to 315 micrograms/ml (p less than 0.05). Plasma fibronectin determinations on malnourished children can serve as an important prognostic marker as well as a reliable indicator of successful therapy and recovery.

Acute Disease