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Biomedical subjects

C J Harrison

Publications and source records attributed to C J Harrison.

At least 109 records · Page 6Linked to original sources
PubMed1993

Adjuvant effects of imiquimod on a herpes simplex virus type 2 glycoprotein vaccine in guinea pigs.

The adjuvant effects of imiquimod for a herpes simplex virus (HSV) vaccine were evaluated. Guinea pigs were immunized with 35 micrograms of lectin-purified HSV-2 glycoproteins 14 and 35 days before intravaginal HSV-2 inoculation. Immunizations were given either alone, with complete Freund's adjuvant, or with three different 5-day regimens of imiquimod. Although immunization alone decreased the severity of the acute disease and viral replication, in two separate experiments, the addition of imiquimod produced further decreases. The addition of subcutaneous imiquimod further decreased viral shedding by > 3 logs on day 1 after virus inoculation (P < .001). All groups that received immunization and imiquimod also developed significantly fewer HSV recurrent lesion days (P < .05-.001) compared to immunization alone. No recurrent lesions were detected in the group that received immunization and subcutaneous imiquimod. Imiquimod enhanced the effectiveness of HSV-2 immunization, especially in reducing recurrent HSV disease, and should be evaluated further as an adjuvant.

Acute Disease↗
PubMed1993

Microbiologic and clinical aspects of a trial of once daily cefixime compared with twice daily cefaclor for treatment of acute otitis media in infants and children.

In this randomized, investigator-blinded multicenter study, tympanocentesis for acute otitis media with effusion in 137 ears from 108 children, 6 months to 12 years of age, revealed 84 definite pathogens and 32 potential pathogens. Twenty-nine aspirates from 23 subjects were sterile. Of the 116 isolates 42 (36%) were Streptococcus pneumoniae, 24 (21%) were Haemophilus influenzae, 9 (8%) were Moraxella catarrhalis, 9 (8%) were Streptococcus pyogenes and 1 (1%) was Staphylococcus aureus. Twenty-two (19%) definite pathogens produced beta-lactamase. Patients were randomized to cefixime (8 mg/kg/day daily) or cefaclor (40 mg/kg/day divided into two doses). Efficacy was determined by pneumatic otoscopy and tympanometry at the end of therapy visit on Days 11 to 14 and up to 4 weeks of follow-up. At end of therapy subjects with definite pathogens exhibited a satisfactory clinical outcome in 26 of 36 (72%) ears for cefaclor and 40 of 48 (83%) ears for cefixime recipients (P = 0.12). For ears with beta-lactamase-producing isolates there were no (0 to 12) cefixime failures but 4 of 10 cefaclor failures (P = 0.03). Diarrhea/loose stools were more frequent in cefixime (16 of 58) than cefaclor (4 of 50) recipients. One cefixime subject required discontinuation of drug. Overall efficacy for treatment of acute otitis media with effusion was not different; however, cefixime appeared more effective for infections caused by beta-lactamase-producing organisms.

Acute Disease↗
PubMed1993

Effect of indomethacin on ultraviolet radiation-induced recurrent herpes simplex virus disease in guinea-pigs.

Exposure to u.v. radiation increases the local level of prostaglandins which may play a role in u.v. radiation-induced herpes simplex virus (HSV) recurrences. We used the guinea-pig model of u.v. radiation-induced recurrent genital HSV-2 disease for examining the effects of indomethacin, a prostaglandin inhibitor, on u.v.-induced recurrences. In the first experiment, performed 100 days after HSV-2 inoculation, treatment with indomethacin for 5 days begun 24 h before u.v.-irradiation decreased the proportion of animals developing HSV disease recurrences from 11/13 (84.6%) to 2/13 (15.4%) (P < 0.001). In the second experiment, performed 135 days after HSV-2 inoculation, treatment with indomethacin for 5 days begun 24 h before u.v.-irradiation decreased the number of animals developing recurrences from 12/21 (57.1%) to 5/21 (23.8%) (P < 0.05). Five days of indomethacin treatment begun 4 h after u.v.-irradiation, however, did not reduce the percentage of animals developing disease recurrences but did decrease the mean number of days with recurrent lesions in animals that developed recurrences. Our data suggest that indomethacin may modify u.v. radiation-induced recurrent lesions by decreasing viral reactivation when given before u.v. radiation exposure or by reducing prostaglandin-induced immunosuppression when given before or after exposure. Future studies are needed for evaluating indomethacin prophylaxis for recurrent HSV disease when prolonged u.v. radiation exposure is anticipated.

Animals↗
PubMed1993

Three cases of the myelodysplastic syndrome with pericentric inversion of chromosome 16.

Inversion of chromosome 16, inv(16)(p13q22), is characteristic of acute myeloid leukaemia (AML) with eosinophilia and is rarely found in the myelodysplastic syndrome (MDS). We report three cases of MDS in which inv(16) was observed. They were classified to FAB subtypes RA, RARS and RAEBT; eosinophilia or abnormal eosinophils were not observed. The disease appeared to be stable in all three patients. MDS with inv(16) without eosinophilia may be a rare subgroup associated with a good prognosis.

Adolescent↗
PubMed1993

Structural abnormalities of the X chromosome in non-Hodgkin's lymphoma.

It has recently been reported that additional X chromosomes occur in over 30% of B-cell non-Hodgkin's lymphomas (NHL), and that monosomy of the X chromosome occurs in 38% of female patients with T-cell leukaemia or lymphoma. These observations have suggested a possible role for the X chromosome in the evolution of NHL. We have now examined 280 cases of NHL, and have identified 19 examples of structurally altered X chromosomes in the malignant cells from 17 of these cases. These abnormalities were mainly characterized by either a translocation involving Xp22, or a translocation/deletion involving Xq28. The relevance of these observations is discussed with respect to other published reports, and together they suggest that lymphoma-associated oncogenes may exist on the X chromosome at bands p22 or q28.

Aneuploidy↗
PubMed1992

Outcome of herpes simplex virus type 2 infection in guinea pigs.

Factors that influence the outcome of genital herpes simplex virus (HSV) infection were explored in a guinea pig model. The viral inoculum required to establish infection in 50% of animals (ID50) was similar for inbred (strain 2) and outbred (Hartley) guinea pigs. However, the viral inoculum required to produce clinical disease in 50% of the animals (CD50) was 10 times greater for strain 2 compared to Hartley animals. HSV infection of both inbred and outbred animals was more likely to result in death of weanling than adult animals. The duration and severity of genital disease and the magnitude of vaginal viral replication were similar for strain 2 and Hartley animals in both young and adult animals. The lethal dose for 50% of animals (LD50) was 100-fold greater than the CD50 for Hartley animals, but the LD50 and the CD50 were equal in strain 2 guinea pigs. Viral cultures of homogenized neural tissues from infected animals revealed that HSV ascended to the level of the temporal cortex in strain 2 guinea pigs while virus was never recovered above the lumbar spinal cord in Hartley animals. Endogenous peripheral blood mononuclear cell-mediated cytolytic activity against HSV-infected targets was greater prior to HSV inoculation in survivors compared to animals that died. A fatal outcome of genital HSV-2 may relate to the failure to limit CNS viral replication. Death is more common among guinea pigs that have low endogenous HSV-directed natural killer activity, such as occurs among strain 2 and young animals whether inbred or outbred.

Administration, Intravaginal↗
PubMed1992

Postnatal encephaloclastic porencephaly--a new lesion?

A previously unrecognised and distinctive pattern of severe brain injury in extreme preterm neonates was observed recently. Fifteen neonates of birth weight 600-1270 g and gestation of 24-32 weeks showed relatively late development on cerebral ultrasound scan of extensive dense and cystic lesions involving the periphery of the brain. The extent of the changes was confirmed at postmortem examination in 11 babies. These changes have been called encephaloclastic porencephaly. The population of babies in whom this has occurred and their clinical outcome has been reviewed, with comparison between the evolution of the ultrasound changes and pathological findings at postmortem examination.

Brain↗
PubMed1992

Waiting times and patient satisfaction in the accident and emergency department.

A survey of the waiting times and patients' opinions of these times was undertaken in a busy district general hospital A&E department. The various components of the overall waiting time are analysed and specific points of the patients' attendance, where waiting times were prolonged, are identified. Standards are derived which is hoped may result in 75% of patients being satisfied with the duration of their wait. The current levels of achievement are compared with these standards. Suggested and actual improvements to the department to improve our performance are described.

Emergency Service, Hospital↗
PubMed1992

Effects of the gonadotrophin-releasing hormone agonist 'Zoladex' upon pituitary and gonadal function in hypogonadal (hpg) male mice: a comparison with normal male and testicular feminized (tfm) mice.

Hypogonadal (hpg) mutant mice, with a congenital deficiency of hypothalamic gonadotrophin-releasing hormone (GnRH), and testicular feminized (tfm) mice, which lack a functional androgen receptor, were used to study the effects of the potent GnRH agonist 'Zoladex' (ICI 118630; D-Ser (Bu(t))6, Azgly10-GnRH) on pituitary and gonadal function. Zoladex (0.5 mg) in a sustained-release lactide-glycolide copolymer depot was administered subcutaneously under anaesthesia and was left in place for 7 days, after which time the effects of the drug upon pituitary and serum gonadotrophin concentrations, glycoprotein hormone subunit mRNAs and testicular morphology were investigated. At the pituitary level, Zoladex treatment resulted in a substantial reduction in LH content in normal males, and LH content was depressed in hpg mice even below the basal levels normally found in these mutants. Pituitary LH content in the Zoladex-treated animals was depressed in the tfm groups, but not to the same levels as those found in the normal and castrated normal mice. Zoladex treatment at the time of castration prevented the post-operative elevation in serum LH associated with castration alone. In the androgen-deficient tfm mouse, Zoladex did not depress the normally elevated serum LH levels. Serum LH in the hpg animals was, in all cases, below the limit of detection of the assay. Pituitary FSH content was depressed into the hpg range in both the normal and castrated animals, but there was no further depression in the hpg mice. The pituitary content was reduced in the tfm mice, again the effects not being as dramatic as in the normal and castrated animals. Serum FSH content, as measured by radioimmunoassay, was depressed by 50% in normal mice; there was no reduction in the hpg mice, however. With regard to pituitary gonadotrophic hormone gene expression, Zoladex administration to normal mice caused a dramatic reduction in LH beta mRNA content, to a level approximating that found in untreated hpg mice. The drug also depressed LH beta mRNA in the castrated group to the hpg range when given at the time of castration, whereas in untreated castrated mice there was a significant increase in LH beta mRNA. In the tfm mouse, which can be considered as a model for long-term failure of androgen feedback, Zoladex again induced a fall in LH beta mRNA, but not to the same extent as in the normal and normal castrated group. Zoladex had no effect on the already low levels of LH beta mRNA found in hpg mice.(ABSTRACT TRUNCATED AT 400 WORDS)

Androgens↗
PubMed1992

Prognostic significance of the balanced t(1;19) and unbalanced der(19)t(1;19) translocations in acute lymphoblastic leukemia.

The recurring chromosomal 1;19 translocation in acute lymphoblastic leukemia (ALL) occurs in balanced t(1;19) (q23;p13) and unbalanced, -19, +der(19)t(1;19)(q23;p13) forms. The clinical features and outcome were compared for 30 patients with the t(1;19) and 36 patients with the der(19) forms. These were 45 children (less than 1-14 years) and 21 adults (15-54 years) (median age 9.0 years), 41 females, 25 males, with median white blood count (WBC) 20.9 x 10(9)/1. Patients were classified by karyotype thus: t(1;19) 11 cases; t(1;19) with additional change (+A) 19 cases; der(19) 17 cases; and der(19) +A, 19 cases. Non-random additional structural abnormalities included involvement of 1q, 6q, i(7q), i(9q), 9p, and 13q. The only significant difference in clinical or blast cell features between patients with the t(1;19) and the der(19) was the greater age of adults with t(1;19) (p less than 0.05). Projected median event-free survival and survival of all cases together was 22 months and greater than 112 months respectively. Neither age nor WBC contributed significantly to prognosis. For patients at all ages, prognosis of der(19) was better than t(1;19). This was statistically significant for event-free and overall survival in childhood (p = 0.02 and p = 0.01 respectively) and was independent of age (p = 0.04 and p = 0.008 respectively) and WBC (p = 0.03 and p = 0.04 respectively). Future studies should examine separately the outcome for patients with the balanced and unbalanced forms of the t(1;19).

Adolescent↗
PubMed1991

Cell-mediated immunologic responses and recurrent genital herpes in the guinea pig. Effects of glycoprotein immunotherapy.

The specific immune alterations associated with HSV recurrences are ill defined although it appears that alterations in cell-mediated immune mechanisms are more likely associated with recurrent disease than humoral immunity. Immunization with HSV glycoproteins B and D (gBgD) after primary HSV infection has reportedly reduced the frequency of recurrences but the mechanisms remain unidentified. We therefore evaluated the effects of immunization with cloned gBgD on selected cell-mediated immune responses and their relationship to recurrent disease by using the guinea pig model of genital HSV-2 infection. In two experiments, immunization with gBgD + CFA on days 21 and 42 after HSV-2 inoculation significantly decreased the number of subsequent recurrent lesion days observed whereas CFA alone had no effect. Immunization with gBgD + CFA increased the lymphoproliferative and in vitro IL-2 response to gBgD more than to whole HSV-2 Ag preparations. Peak responses were observed 2 wk after the second immunization. The HSV-specific cytolytic response was also persistently increased beginning 1 wk after the first immunization. Analysis including both untreated and gBgD-immunized animals revealed that recurrent lesion days were inversely correlated to the IL-2 response to whole HSV-2 Ag (p less than 0.0001), the IL-2 response to gBgD (p = 0.0004), and the HSV-specific cytolytic response (p = 0.005 and 0.003 in two experiments, respectively). When the untreated group was analyzed separately, only the IL-2 response to whole HSV-2 Ag correlated to recurrences (p = 0.007). HSV glycoprotein immunization may increase IL-2 or other cytokines secreted by HSV-sensitized T cells increasing critical immune responses, such as NK- or lymphokine-activated killer-mediated cytolysis, that could eliminate the reactivated virus before the development of clinically apparent lesions.

Animals↗
PubMed1991

Tracheal granulation tissue. A study of bacteriology.

We prospectively examined 19 patients (21 laryngotracheal reconstructions) over a 6-month period to evaluate the bacteriology of granulation tissue present at the time of Teflon stent removal and at the first laryngoscopy several weeks later. The most frequently recovered isolates were viridans streptococci, Pseudomonas aeruginosa, nonhemolytic Streptococcus, and Staphylococcus aureus. All but one positive culture were polymicrobial. The amount of tissue did not correlate with the duration of stenting and the amount of granulation tissue and number of organisms decreased after stent removal. Further prospective study of the most appropriate antimicrobial therapy is needed.

Bacteria↗
PubMed1991

Low maternal CD4 count at inception of gestational cytomegalovirus (CMV) infection and impaired humoral response: effect on congenital CMV infection in the guinea pig.

In humans, the rate and clinical expression of disease in congenitally cytomegalovirus (CMV)-infected infants is modified by maternal immunity to CMV. We used the guinea pig model of congenital CMV infection to compare maternal CD4+ T-cell numbers in nonpregnant animals to those in pregnant dams just before and 7-14 days after inoculation with guinea pig CMV (gpCMV) very early, early, or late in gestation. We also examined ELISA antibody responses to gpCMV in the inoculated nonpregnant and pregnant animals. When compared to nonpregnant uninfected animals, CD4 counts were lower in very early and in late uninfected gestation. CD4 counts also dropped further in the postinoculation period. Compared to nonpregnant gpCMV-inoculated animals, initial antibody responses to gpCMV were also decreased in gpCMV-infected pregnant dams. The group of dams inoculated very early in pregnancy experienced delays in seroconversion to gpCMV, persisting low titers throughout gestation, in utero fetal resorptions, and CNS-infected pups. The group of dams inoculated late in gestation had the lowest geometric mean titers at delivery (almost 50% with no detectable antibody) and a high rate of vertical gpCMV transmission and postnatal pup death. Significantly lower rates of both congenital infection and postnatal pup deaths were observed in litters of late gestation-infected dams that had gpCMV antibody at delivery. Thus, decreased circulating maternal CD4+ T cells very early and late in gestation were further decreased after gpCMV inoculation and were associated with delayed and depressed maternal antibody responses, all of which were associated with poor outcome after primary maternal gpCMV infection, the expression of which varied by time in pregnancy when gpCMV was acquired.

Animals↗
PubMed1991

Alveolar rhabdomyosarcoma with del(13q14).

We report a case of disseminated alveolar rhabdomyosarcoma, where chromosome analysis showed a deletion of chromosome 13(q14). This breakpoint is involved in the t(2;13)(q37;q14) previously reported in cases of rhabdomyosarcoma, but this is the first reported case in whom this deletion occurs without involvement of chromosome 2. The possible oncogenic role of the retinoblastoma (RB1) gene located at the breakpoint is discussed.

Adult↗
PubMed1991

Effects of cytokines and R-837, a cytokine inducer, on UV-irradiation augmented recurrent genital herpes in guinea pigs.

We have recently reported that latently HSV-2-infected guinea pigs exhibit a three- to four-fold increase in recurrent lesions after exposure to ultraviolet radiation (UV), allowing rapid evaluation of antiviral drugs in treating recurrent HSV disease. In this report we examine the effect of alpha interferon (IFN-alpha), interleukin-2 (IL-2), and a cytokine inducer (R-837) on UV-induced recurrent genital herpes. We have previously shown that topical R-837 is a biologic response modifier with no in vitro anti-HSV activity, but with potent anti-HSV activity in vivo due to cytokine induction and enhancement of cell-mediated immune responses. Three-day regimens of intravaginal R-837, or five-day intraperitoneal (i.p.) administration of IFN-alpha or of IL-2 each significantly reduced recurrent genital HSV-2 disease that occurred within 7 days of UV exposure, suggesting that cytokines or cytokine inducers may be useful in the treatment of recurrent HSV disease. This model using ultraviolet radiation to induce recurrent herpes simplex virus infection proved useful in the evaluation of immunoactive agents as putative antiviral drugs.

Adjuvants, Immunologic↗