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Biomedical subjects

J Ward

Publications and source records attributed to J Ward.

At least 289 records · Page 16Linked to original sources

Functional activities of human antibody induced by the capsular polysaccharide or polysaccharide-conjugate vaccines against Haemophilus influenzae type b.

To determine the in vitro and in vivo activity of human antibody induced by different Haemophilus influenzae type b (Hib) vaccines, pooled human antisera obtained from adults immunized with either polyribosyl ribitol phosphate (PRP) or PRP-conjugated with diphtheria toxoid (PRP-D) vaccines were evaluated for opsonic and protective activity against Hib. In vitro, opsonophagocytic studies revealed that PRP-D induced antisera were approximately 2.5-fold more effective than PRP-induced antisera in supporting neutrophil-mediated killing of an Hib strain. In vivo studies using the infant rat model or Hib disease revealed that the decay of PRP antibody was similar with PRP or PRP-D induced antisera in unchallenged rats. However, in infant rats challenged with Hib, the PRP induced antibody decayed more rapidly than the PRP-D induced antibody as shown by significantly shorter half-life of the former. The protective efficacy was significantly greater with the PRP-D induced antisera than with the PRP induced antisera. This finding was shown by the significantly lower incidence of bacteraemia and the 5-fold lower dose of antibody required for 50% protection against bacteraemia in rats receiving the PRP-D induced antisera. The findings suggest that antibody to PRP induced by PRP-D vaccine is more opsonic and protective against Hib, and also decays more slowly in infant rats challenged with Hib than does antibody induced by PRP vaccine. Further studies are needed to elucidate the reason(s) for this difference in functional activity and in half-life of PRP antibody induced by PRP or by PRP-D vaccines.

Adult↗

Multi-centre general practitioner comparative study of controlled-release ('Valrelease') and conventional ('Valium') forms of diazepam in patients suffering from anxiety.

A multi-centre, double-blind, parallel group study was carried out in 114 patients with an anxiety disorder to compare the effectiveness of diazepam given as 5 mg 3-times daily or as a once-daily 10 mg dose of a controlled-release formulation designed to provide smooth drug concentrations over about 24 hours, without the heavy sedation caused by a high initial peak. Patients were allocated at random to receive one or other dosage regimen for 1 week and treatment could be continued for a further week if necessary. Clinical assessments of response to treatment showed that whilst both formulations were equally effective in providing symptomatic improvement, a much higher proportion of patients on controlled-release diazepam were ready to terminate treatment after 1 week, having attained the desired relief of symptoms. Moreover, as indicated by patient diary records, significantly fewer patients on the controlled-release formulation complained of drowsiness in the morning and evening.

Anxiety Disorders↗

An assay of membrane-bound Trypanosoma brucei phospholipase using an integral membrane protein substrate and detergent phase separation.

The technique of phase separation in a solution of the non-ionic detergent Triton X-114 was used to measure the enzymatic conversion of a membrane protein to a soluble product via removal of a hydrophobic moiety. The substrate was the major surface protein (p63), of Leishmania promastigotes and the enzyme was a phospholipase C purified from Trypanosoma brucei. This membrane-bound enzyme is responsible for the cleavage of the hydrophobic lipid membrane anchor of the variant surface glycoprotein (VSG), of T. brucei. The assay is fast, simple and uses small amounts of reagents. It has been used to determine the pH optimum, thermal resistance, and the sensitivity to inhibitors of the trypanosomal phospholipase.

Animals↗

Blood volume and red cell space in tissues of the rainbow trout, Salmo gairdneri.

1. Whole body blood volume and red cell space of 22 tissues were measured in unanesthetized rainbow trout at 4, 12, 30, 60, 150 and 240 min after dorsal aortic injection of 51Cr-labeled red blood cells. 2. Apparent blood volume decreased during the initial 30 min after injection and increased thereafter. At 240 min the blood volume was 33.5 +/- 3.1 ml/kg body wt. 3. Tissue red cell space varied as a function of the interval between labeled red cell injection and tissue collection. Red cell space was highest in spleen followed by heart, kidney and liver. Lowest red cell spaces were found in stomach and red and white skeletal muscle. 4. Variability in blood volume and tissue red cell space over time suggests that caution should be exercised in the design of experiments that employ indicator dilution measurements to measure vascular volumes.

Animals↗

Safety and immunogenicity of Haemophilus influenzae type b polysaccharide-diphtheria toxoid conjugate vaccine (PRP-D) in infants.

Safety and immunogenicity of a Haemophilus influenzae type b polysaccharide-diphtheria toxoid conjugate vaccine (PRP-D) was evaluated in infants seven to 14 months of age. PRP-D (80% of subjects) or saline placebo (20%) was randomly and blindly administered (two doses separated by two months). Incidence of mild reactions lasting less than 48 hr did not differ significantly between the placebo and vaccine recipients. Preimmunization levels of antibody to PRP were less than or equal to 0.15 micrograms/ml in 97% of subjects. A twofold increase in antibody concentration occurred in 88% of subjects following the first dose and in 99% following the second dose of vaccine. No change occurred in placebo recipients. Mean level of antibody and percentage of subjects with levels of antibody greater than or equal to 1 microgram/ml after vaccination increased with increasing age. Responses were related to vaccine lot but not to sex, race, or geographic location. Two doses of PRP-D in infants seven months of age and older induced antibody levels equal to or greater than levels in infants 24 months of age given the polysaccharide alone.

Antibodies, Bacterial↗

Recurrent invasive Haemophilus influenzae type b disease in Alaskan Natives.

Alaskan Natives (Indians and Eskimos) have an extraordinary incidence of invasive Haemophilus influenzae type b (Hib) disease (500 cases/100,000 children younger than 5 years of age) and also an increased incidence of recurrent disease. However, the incidence of primary Hib disease and recurrent disease are not excessive in non-Native children in Alaska (mainly Caucasian). Twelve recurrent cases in Alaskan Natives were studied, 10 of which were detected in surveillance activities between 1971 and 1984. These recurrent episodes occurred 23 to 197 days after the initial episodes (median, 51 days); the overall rate of recurrent disease was 3.5%. The ages of the patients with recurrent disease were significantly younger than single episode cases. To determine if disease recurrence was a manifestation of the high disease incidence and earlier age at onset of disease, we calculated an expected number of recurrent cases for our study population, based on the incidence observed in children with first episodes and the period of observed follow-up. The expected number of recurrent cases was only 1.9, significantly fewer than the 10 observed, indicating that age and the high incidence of disease alone were not the only factors contributing to the recurrent disease. No other significant clinical or epidemiologic risk factors could be identified. Patients who develop recurrent invasive Hib disease may represent a subset of this population with unusual disease susceptibility.

Alaska↗

Newer Haemophilus influenzae type b vaccines and passive prophylaxis.

PRP-protein conjugate vaccines may prove to be a prototype of a new generation of bacterial vaccines for the prevention of diseases caused by encapsulated bacteria, such as pneumococci, meningococci and Group B streptococci, as well as Hib. These diseases often strike the very young, the very old and individuals with compromised immunity. These vaccines have been "engineered" to maximize immune recognition and response. It is hoped that these vaccines will be adequate to control or possibly eradicate Hib and other invasive bacterial diseases. For high risk populations unable to respond to the vaccines, passive prophylaxis may have a role.

Bacterial Capsules↗

Immediate breast reconstruction with tissue expansion.

Between October of 1983 and June of 1985, 31 patients underwent primary breast reconstruction with tissue expansion. Tissue expansion was utilized for breast reconstruction when the remaining muscle and skin following modified radical mastectomy was insufficient to accommodate a prosthesis that matched in size and shape the opposite breast. All expanders were placed beneath an investing muscular pocket created by elevating the pectoralis major and serratus anterior. Postoperative expansion began within 1 week, and the breast was expanded to double the volume of the opposite breast. Twenty-two patients have completed their reconstruction with a mean follow-up in 7 months. There were nine complications, including five deflations and four infections. All patients have remained Baker I or Baker II. Creating ptosis to match the breast was accomplished by placing the expander below the rectus fascia and superiorly advancing this expanded tissue at the time of prosthesis placement. Primary breast reconstruction with tissue expansion following modified radical mastectomy is safe, simple, and produces a breast with excellent shape, size, texture, and patient satisfaction.

Breast↗

An evaluation of cell therapy in Down syndrome.

A group of children with Down syndrome who were being treated with cell therapy was matched for age and sex with an untreated control group. Comparisons were made between the groups with respect to a number of developmental and physical variables which have been reported to be influenced by cell therapy. Of 55 comparisons made between treated and control groups, two differences were statistically significant. This study failed to show sufficient significant results for the treatment to be regarded as effective.

Cell Extracts↗

Candida parapsilosis fungemia associated with parenteral nutrition and contaminated blood pressure transducers.

During the period September 1983 through May 1985, Candida parapsilosis was isolated from intravascular sites (blood or vascular catheter tips) in 12 patients at a pediatric hospital. Of 205 patients with cultures of any site positive for Candida species, 32 (16%) had cultures positive for C. parapsilosis. In contrast, of 23 patients with intravascular cultures positive for Candida species, 12 (51%) had cultures positive for C. parapsilosis (P less than 0.001, Fisher's exact test). The 12 patients with intravascular cultures positive for C. parapsilosis were more likely to have received central venous nutrition therapy (10 of 12 versus 7 of 23; P less than 0.01, Mantel-Haenzel chi-square test) and had a longer duration of exposure to blood pressure transducers (P less than 0.08, paired t test) than the 23 ward- and age-matched controls. C. parapsilosis was isolated from 11 (32%) of 34 in-use and stored blood pressure transducers. After ethylene oxide sterilization of blood pressure transducers was begun, in-use pressure transducers showed no growth of C. parapsilosis. This study emphasizes the role of C. parapsilosis as a nosocomial pathogen associated with invasive devices and parenteral nutrition; it also emphasizes the importance of adhering to recommended procedures for sterilizing blood pressure transducers.

Adolescent↗

Ampicillin-chloramphenicol-resistant Haemophilus influenzae: plasmid-mediated resistance in bacterial meningitis.

A 4-month-old infant with congenital heart disease and sepsis and arthritis, and subsequently meningitis, caused by an antibiotic-resistant strain of Haemophilus influenzae type b, failed to respond to sequential therapy with ampicillin and trimethoprim/sulfamethoxazole. Following treatment with ceftizoxime, the infant was well for 42 days, until he returned to the hospital and died. A total of 10 Haemophilus influenzae type b isolates, all outer membrane protein subtype 51, was isolated from the pretreatment blood and synovium, cerebrospinal fluid and subdural fluids, and the petrous pyramids at autopsy. Pretreatment isolates had no detectable plasmid DNA, chloramphenicol acetyltransferase or beta-lactamase; the minimal inhibitory concentration for ampicillin (AM) and chloramphenicol (CM) was 0.2 and 0.8 microgram/ml, respectively. However, all cerebrospinal fluid isolates had a 42-44 mD plasmid and produced chloramphenicol acetyltransferase and beta-lactamase; the minimal inhibitory concentration of these isolates to AM and CM were 12.5 and 25 micrograms/ml, respectively, and were also resistant to tetracycline and sulfonamide. Resistance to AM and CM was cotransferred by filter-mating conjugation at a frequency of one to two transconjugants per 10(5) to an Rd haemophilus recipient. Posttreatment isolates from the petrous pyramids also were resistant to AM and CM and produced chloramphenicol acetyltransferase and beta-lactamase activity, but had no plasmid DNA. These findings and data from genetic studies suggested that plasmid-bearing antibiotic-resistant Haemophilus influenzae type b was selected from a heterogenous population, and that the AM/CM resistance transposons were incorporated into the bacterial chromosome.

Ampicillin Resistance↗

Sensory perception threshold measurement: an evaluation of semiobjective testing devices.

Five semiobjective devices for testing sensory perception thresholds were concomitantly used on 36 normal subjects to determine normal threshold values, intersubject variability, and their correlation with age. The five devices include the Semmes-Weinstein monofilament (touch); three-point esthesiometer (two-point discrimination); Pfizer thermal tester (temperature); biothesiometer (vibration); and Optacon tactile tester (vibration). Each subject was tested at 12 upper extremity (UE) and ten lower extremity (LE) sites. The threshold was determined by the two-alternative forced choice method. Results showed that the mean threshold for each sensory perception modality in the UE sites was significantly lower than in the LE sites. The means of distally located sites for two-point discrimination and vibration thresholds were significantly lower than the means of the proximal sites in the UE. In the LE, touch perception threshold was significantly higher distally than proximally. Distally located nerves (median and ulnar) showed lower mean threshold values than proximally located nerves for two-point discrimination. There were also similar findings for the other sensory modalities in the UE and LE. The mean threshold of dermatomes showed significant variation across the trials for two-point discrimination and vibration sensation. Distally located dermatomes showed lower threshold values than those located proximally. The means of most sites tested for each sensory modality (except vibration tested by the Optacon) showed correlation with age. There was no difference in threshold values between men and women for any sensory modality. The mean values of standard deviation were provided for each peripheral sensory nerve and dermatome.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Preliminary crystallographic studies on bovine lactoferrin.

The purification of bovine lactoferrin, its crystallization at low ionic strength, and preliminary X-ray crystallographic data are reported. The crystals, which grow from a two-phase system, are radiation-stable and suitable for a medium-resolution X-ray analysis. They are orthorhombic, space group P2(1)2(1)2(1), with cell dimensions a = 138.4 A, b = 87.1 A, c = 73.6 A, and one protein molecule in the asymmetric unit.

Animals↗

Purification and characterisation of membrane-form variant surface glycoproteins of Trypanosoma brucei.

Membrane-form variant surface glycoprotein of Trypanosoma brucei can be prepared in the presence of para-chloromercuriphenylsulphonic acid. The membrane-bound enzyme that usually cleaves a lipid from this glycoprotein, thus producing the soluble variant surface glycoprotein, is inhibited by a range of sulphydryl reagents. The effect of such inhibitors, both on cell lysates and on semi-purified enzyme, reveals that the enzyme may have a sulphydryl at or near its active site. Fatty acid analysis and isoelectric point measurements of membrane form and soluble form are presented.

4-Chloromercuribenzenesulfonate↗