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Biomedical subjects

J W Ward

Publications and source records attributed to J W Ward.

At least 91 records · Page 5Linked to original sources
PubMed1989

Biologic factors in the sexual transmission of human immunodeficiency virus.

The probability that any single episode of genital-genital or anogenital sexual intercourse will result in transmission of HIV may be determined by multiple biologic factors of the infectious person, the virus itself, and the exposed susceptible person. Some of these factors are known or suspected (figure 1), and they may explain observed differences in the sexual transmission of HIV in different parts of the world, notably in Africa, where genital ulcerative disease is probably influencing the epidemiology of HIV. Several studies have shown that infection in partners of HIV-infected persons is not determined solely by numbers of sexual encounters; on the contrary, HIV-infected partners have usually had fewer sexual encounters with infectious mates than have noninfected partners. Thus, sexually active persons should be cautioned that, to our knowledge, there are no nonsusceptible persons and that any single unprotected sexual encounter may lead to HIV transmission. Research into biologic factors that modulate HIV transmission continues to be hampered by difficulties in identifying HIV transmitters and nontransmitters, infective and noninfective variants of HIV (if the latter exist in vivo), and persons relatively more or less susceptible to HIV infection. However, as the number of partner studies and the number of those enrolled in them increase, a progressively clearer idea of the biologic determinants of sexual transmission of HIV should emerge.

Acquired Immunodeficiency Syndrome↗
PubMed1989

The epidemiology of HIV transmission among paid plasma donors, Mexico City, Mexico.

Screening of blood product donations for antibody to HIV began in Mexico in May 1986. From June to October 1986, the HIV cumulative seroprevalence increased from 6.3 to 9.2% in a commercial plasma collection center. Of the 281 people who donated the antibody-positive units, 62 (22.1%) had documented seroconversion during these 5 months. An epidemiologic study of 54 seropositive and 58 seronegative donors was carried out. The HIV serologic status did not change in any of these donors after repeat testing. Only 13.0% of the seropositives and 15.5% of the seronegatives had any of the known risk factors for AIDS. There was a direct relationship between frequency of plasma donation and the risk of being seropositive. A survey of employees disclosed the frequent re-use of disposable blood collection equipment. We conclude that HIV transmission had probably occurred in this plasma collection center.

Adult↗
PubMed1989

Variable metabolism of pinacidil: lack of correlation with the debrisoquine and trimethylamine C- and N-oxidative polymorphisms.

1. The urinary excretion of pinacidil and its N-oxide in man was found to vary over a five-fold range. 2. Studies in individuals with inherited deficiencies for C-hydroxylation (debrisoquine type) and trimethylamine N-oxidation showed that the N-oxidation of pinacidil did not co-segregate with these oxidative polymorphisms. 3. It is concluded that the variable N-oxidation of pinacidil is most likely to be due to variations in the activity of the P-450 isozymes rather than in the microsomal flavoprotein containing mixed-function amine oxidase of Ziegler which is considered to be responsible for the N-oxidation of trimethylamine.

Adult↗
PubMed1989

Clinical and therapeutic monitoring of epilepsy in a mental handicap unit.

Within a group of hospitals for the mentally handicapped serving the Leicestershire district, a cohort of 215 epileptic patients was identified, who were followed up for four years. The anticonvulsant medication of each patient was reviewed regularly until an optimal balance between seizure control, absence of medication side-effects, and reduction of polypharmacy was attained. After four years 172 patients remained in the study. A significant reduction in polypharmacy was attained overall. Some groups of patients showed a significant reduction in the frequency of seizures, while a small group of patients with frequent seizures remained difficult to control.

Adult↗
PubMed1988

Transmission of human immunodeficiency virus (HIV) by blood transfusions screened as negative for HIV antibody.

Since early 1985, blood donations in the United States have been screened for antibody to human immunodeficiency virus (HIV). To identify instances of HIV transmission by antibody-negative donations, we investigated 13 persons seropositive for HIV who had received blood from 7 donors who were screened as negative for HIV antibody at the time of donation. Twelve of the 13 recipients had no identifiable risk factors for HIV infection other than the transfusions they had received. On evaluation 8 to 20 months after transfusion, HIV-related illnesses had developed in three recipients, and the acquired immunodeficiency syndrome had developed in one. All seven donors were found to be infected with HIV. On interview, six reported a risk factor for HIV infection, and five had engaged in high-risk activities or had had an illness suggestive of acute retroviral syndrome within the four months preceding their HIV-seronegative donation. Thus, these donors had apparently been infected only recently, and so were negative at the time of blood donation according to available antibody tests. We conclude that there is a small but identifiable risk of HIV infection for recipients of screened blood. To minimize this risk, the reasons for deferral of donation need to be communicated more effectively to blood donors who are at high risk of HIV infection, and new assays that detect HIV infection earlier should be evaluated for their effectiveness in screening donated blood.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Effects of food on the bioavailability of sustained-release pinacidil in humans.

The effects of a standard breakfast meal on the bioavailability of a sustained-release tablet formulation of pinacidil [(+/-)-2-cyano-1- (4-pyridyl)-3-(1,2,2-trimethylpropyl)guanidine monohydrate) were investigated in eight healthy volunteers. Concomitant food intake resulted in significantly increased maximum measured serum pinacidil concentrations, Cmax, (172 +/- 21 versus 102 +/- 49 ng/mL, p less than 0.05), and relative bioavailability, measured as AUCo-infinity (904 +/- 189 versus 697 +/- 279 ng.h/mL, p less than 0.05). The time to maximum serum concentration (tmax) was not affected by food (2.3 +/- 1.3 versus 3.3 +/- 1.2 h, p greater than 0.05), and the terminal elimination half-life, (t1/2z) was significantly decreased (4.7 +/- 2.2 versus 2.3 +/- 0.4 h, p less than 0.05).

Adult↗
PubMed1988

Accumulation of pinacidil N-oxide during chronic treatment with pinacidil.

The effects of acute and chronic administration of a slow-release preparation of pinacidil have been studied in eight normotensive volunteers aged 40-57 years. Continuous administration of 20 mg b.i.d. pinacidil had no effect on serum pinacidil concentrations measured as AUC (0-9 h), but accumulation of the principal metabolite, pinacidil pyridine-N-oxide was found to occur. There were no significant changes in erect and supine blood pressure and heart rate from the pretreatment levels on days 1,15 or 29. Chronic administration of pinacidil caused a significant increase in weight over the total period of study. There were also significant changes in mean sodium (+2.38 mmol/l) and alkaline phosphatase (+15.75 iU/l) from the start to the end of pinacidil therapy but values were within the normal ranges, except for one alkaline phosphatase. There were significant changes in the following haematological parameters over the period of pinacidil therapy; leukocytes (-1.49 x 10(9)/l), haemoglobin (-0.56 g/dl), MCH (-1.1 pg), MCHC (-1.22 g/dl), platelet MCV (-0.90 fl).

Adult↗
PubMed1988

Vascular anatomy of the upper extremity muscles.

This study delineates the vascular anatomy of the upper extremity with particular attention toward the size, location, and number of vascular pedicles supplying each muscle. Ten cadaver upper extremities were dissected. A total of 440 muscles and 2209 pedicles were identified. The major "named" arterial source, number of pedicles, and pattern of perfusion for each muscle were delineated. Detailed description of the vascular anatomy of muscles commonly used for tendon transfer and local flaps is presented. The potential use of the coracobrachialis flap for contouring the infraclavicular area is elucidated. The anatomic bases of the anconeus and flexor carpi ulnaris flaps are confirmed. The radial and ulnar arteries may be used as microvascular donor or recipient vessels without compromising forearm muscle perfusion.

Adult↗
PubMed1987

Serologic markers after the transplantation of corneas from donors infected with human immunodeficiency virus.

Four corneas from two cadavers that later had positive test results on enzyme-linked immunosorbent assays and Western blot analysis for antibodies against the human immunodeficiency virus were inadvertently transplanted to recipients who were without known risk of human immunodeficiency virus infection. We performed serial studies of serologic markers of human immunodeficiency virus infection in the cornea recipients and assayed reverse transcriptase levels of their mixed lymphocyte cultures. The four cornea transplant recipients were followed up for 130, 152, 397, and 440 days, respectively, and the results on all serologic tests and reverse transcriptase assays remain negative.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Effects of formulation on the pharmacokinetics of orally administered pinacidil in humans.

Serum concentrations, relative bioavailability, and urinary excretion of pinacidil [(+/-)-2-cyano-1-(4-pyridyl)-3-(1,2,2-trimethylpropyl) guanidine monohydrate] from two sustained-release oral formulations (tablet and capsule) were compared in 12 healthy volunteers. Maximum measured serum concentrations (Cmax) from the sustained-release tablet and capsule did not differ significantly (75 +/- 17 versus 70 +/- 14 ng/mL, p greater than 0.05), but the time to achieve maximum concentration (tmax), was longer for the capsule (2.4 +/- 1.8 versus 0.98 +/- 0.5 h, p less than 0.05). There was no significant difference in bioavailability between the formulations, as measured by the area under the concentration-time curve (AUC0-8 h; 279 +/- 99 versus 311 +/- 85 ng.h/mL, p greater than 0.05). Twenty-four hour urinary excretion of both pinacidil and its major metabolite, pinacidil pyridine-N-oxide, was similar for both tablet and capsule preparations (3.9 +/- 1.2 and 55 +/- 19% versus 4.4 +/- 1.0 and 55 +/- 14%, respectively, of the administered dose, p greater than 0.05).

Administration, Oral↗
PubMed1987

The analgesic and antiinflammatory activity and pharmacologic properties of bromfenac.

Bromfenac sodium (2-amino-3-(4-bromobenzoyl)benzeneacetic acid sodium salt sesquihydrate, AHR-10282B) is a potent long-acting, peripheral, analgesic compound possessing antiinflammatory, antipyretic, and prostaglandin synthetase-inhibiting properties. In the acetylcholine abdominal constriction assay in mice, bromfenac (bromfenac sodium) by the oral route at pretreatment times of 10, 20 and 300 min was respectively 3.7, 6.5 and 2.9 times more potent than zomepirac and 3.4, 6.6., and 44.2 times more potent than suprofen. In dogs bromfenac when given orally was 5.8 times more potent than zomepirac in blocking the nociceptive response to bradykinin. Naloxone did not alter the analgesic properties of bromfenac in mice; and after repeated administration, tolerance to analgesia did not develop. Bromfenac, given orally, was more potent than indometacin in suppressing acute (7.5-20 times) and chronic (3.8 times) inflammation. The gastric and intestinal toxicity potencies of bromfenac, given orally, were comparable with and 1.8 times more potent than indometacin, respectively. Bromfenac was 6.1 to 32.8 times more potent than indometacin in inhibiting the formation of prostaglandin E2 and F2 alpha from microsomes of bovine seminal vesicles, rabbit uteri, and rabbit renal medullae; but it did not block the direct action of prostaglandin E1 (abdominal constriction) and prostaglandin F2 alpha (contraction of the uterus). Bromfenac produced no unwanted central nervous system, cardiovascular, or autonomic effects.

Acetylcholine↗
PubMed1986

Laboratory and epidemiologic evaluation of an enzyme immunoassay for antibodies to HTLV-III.

The enzyme immunoassays (EIAs) for antibody to human T-cell lymphotropic virus type III (HTLV-III) were rapidly adopted for screening donated blood and plasma. To evaluate the significance of a positive EIA reaction, test performance was examined in a blood bank screening program. Specimens were tested by EIA, Western blot assay, and HTLV-III/lymphadenopathy-associated virus (LAV) culture. The EIA was positive in 0.25% of 67 190 blood donations. Specimens were categorized and 57.3% had low (weak) reactivity, 12.7% had moderate reactivity, and 30.0% had high reactivity. Highly reactive specimens were strongly associated with a positive Western blot or culture (86.7%) in contrast to moderately and weakly reactive specimens (1.9%). Twenty-five of 29 donors interviewed with a highly reactive EIA had risk factors for HTLV-III/LAV infection. Risk factors were not identified for 74 of 75 interviewed donors with specimens of lower reactivity. The minimum calculated specificity was 99.82%. The use of the HTLV-III EIA has virtually eliminated the use of blood and plasma from HTLV-III/LAV infected donors.

Adult↗
PubMed1986

The pharmacokinetics of timegadine and two of its metabolites after multiple oral dosing, and the effects of concomitant administration of ibuprofen.

A 250 mg tablet of timegadine was given twice daily for 15 days to 13 healthy volunteers. On Day 16 a single morning dose of timegadine was supplemented by two 200 mg tablets of a proprietary brand of ibuprofen. Serum concentrations of timegadine were measured by high pressure liquid chromatography, and steady state was achieved between Days 5 and 8. Serum concentrations of two metabolites of timegadine, MI and MII were measured by thin layer chromatography by Leo Pharmaceutical Products, Denmark. Ibuprofen did not significantly affect the serum half-time of timegadine, but did reduce the maximum measured serum timegadine concentration, the area under the serum concentration versus time curve and the time to achieve maximum measured serum concentration. Serum liver enzymes remained within the normal ranges and there were no changes in hepatic microsomal enzyme activity as assessed by urinary excretion of D-glucaric acid.

Adult↗
PubMed1986

Antagonism of cisplatin-induced emesis by metoclopramide and dazopride through enhancement of gastric motility.

The antiemetic activity, gastric motor activity, and dopamine receptor effects of metoclopramide, dazopride, and sulpiride were assessed to establish if enhancement of gastric motility or antagonism of central dopamine receptors is the predominant action for drug-induced suppression of cisplatin-induced emesis. Emesis produced in dogs by cisplatin is antagonized by metoclopramide and dazopride. The antiemetic actions of metoclopramide and dazopride are associated with their ability to enhance gastric motor activity. Dazopride, unlike metoclopramide, has minimal dopamine receptor antagonist properties. Sulpiride is a potent dopamine receptor antagonist; however, it had no effect on the stomach and was ineffective in suppressing cisplatin-induced emesis.

Animals↗