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Biomedical subjects

J B Ziegler

Publications and source records attributed to J B Ziegler.

At least 37 records · Page 2Linked to original sources
PubMed1996

Health care and its costs for children with perinatally acquired HIV infection.

OBJECTIVE: To describe survival patterns, use of health services and related costs for Australian children with perinatally acquired human immunodeficiency virus (HIV) infection. METHODOLOGY: A retrospective cross-sectional survey was made of 20 children with HIV infection (91% of those diagnosed) and 13 children with maternal antibodies who subsequently seroreverted, treated at 10 medical centres. Details of disease progression and use of health services were obtained from hospital medical records. Monthly costs for three phases of infection were estimated by linking service usage rates with estimates of the unit cost of each service. The average lifetime cost was estimated by combining monthly costs and phase duration estimates from the literature. RESULTS: Patterns of disease progression were similar to those reported internationally, with a median survival of 8 years. Use of health services increased with severity of illness. Mean monthly costs were $120 per month (1992 Australian dollars) for children with maternal antibodies who subsequently seroreverted, $320 per month for children with HIV infection but no acquired immunodeficiency syndrome (AIDS)-defining illness, and $1830 per month for children with AIDS. The present value of total lifetime cost for a child with HIV infection was $48174, 46% of which was for treatment of AIDS. DISCUSSION: The mean lifetime cost for a perinatally infected child was just over half that for a man with HIV in Australia. Health service usage and costs were lower for Australian than American children with HIV.

Australia↗
PubMed1996

Late diagnosis and correction of purine nucleoside phosphorylase deficiency with allogeneic bone marrow transplantation.

A 5-year-old boy with spastic quadriplegia, T cell immunodeficiency, hypouricemia and immune cytopenias from age 8 months, was found to have purine nucleoside phosphorylase (PNP) deficiency, and developed chronic lung disease. Successful matched sibling BMT for PNP deficiency has not previously been reported. BMT using marrow from an HLA-identical sibling donor was performed after conditioning with busulfan (16 mg/kg), cyclophosphamide (200 mg/kg), melphalan (90 mg/m2) and anti-thymocyte globulin (36 mg/kg). T lymphocyte numbers, PNP activity and uric acid levels rapidly improved and he remains well 12 months after transplant.

Bone Marrow Transplantation↗
PubMed1996

Successful bone marrow transplantation in a child with X-linked chronic granulomatous disease.

A 16-month-old Aboriginal boy was diagnosed with chronic granulomatous disease (CGD) when he presented with frequent significant infections from the age of 12 months. BMT was performed from a HLA-matched sibling after conditioning with busulphan, cyclophosphamide, etoposide and antithymocyte globulin. A small bowel obstruction developed in the first week and settled with conservative treatment. VOD occurred in the third week, resolving after treatment with tissue plasminogen activator. Sustained engraftment has occurred, as indicated by return of the nitroblue tetrazolium (NBT) test to normal when performed at 11 weeks and 7 months post-BMT. No further infections have occurred. BMT can be successfully performed for CGD. Complications occurring post-BMT may be related to the underlying disease (CGD). BMT remains an attractive option for CGD in children who have a matched sibling donor.

Bone Marrow Transplantation↗
PubMed1994

Decay of transplacental human immunodeficiency virus type 1 antibodies in neonates and infants.

Transplacental human immunodeficiency virus (HIV) antibodies from 11 uninfected and 3 infected infants of HIV-seropositive mothers were measured using end point titration of twofold dilutions of sera by a particle-agglutination method. Four or more sequential serum samples from each infant were collected between birth and age > or = 14 months and analyzed. Linear regression of log2 antibody titers of uninfected infants plotted against age (days) showed an exponential decay in maternal HIV antibodies. The mean half-life of passive HIV antibodies was 23.1 +/- SD 4.2 days (range, 18.2-29.3; 95% confidence interval, 20.2-26.0). The median age of clearance of maternal HIV antibodies was 13.3 months (range, 10.4-15.6). A model assuming first-order exponential decay and production of HIV antibodies was fitted to the time course of antibody titers of the infected infants. Minimal titers in each infected infant occurred at 5.5, 4.9, and 4.0 months, and doubling times of HIV antibodies from that point ranged from 16.8 to 31.4 days.

Agglutination Tests↗
PubMed1994

Early detection of human immunodeficiency virus type 1 infection in Australian infants at risk of perinatal infection and factors affecting transmission.

The earliest, most reliable methods for detecting human immunodeficiency virus type 1 (HIV-1) infection in infants at risk of perinatal HIV-1 and risks for transmission were investigated. Fifteen infants were followed prospectively from birth to age 21 to 48 months. Epidemiologic data on mothers during pregnancy were documented, and maternal proviral load (by quantitative polymerase chain reaction) and viral phenotype by HIV isolation were performed. Infants were assessed clinically and HIV isolation, HIV p24 antigen, polymerase chain reaction and total serum immunoglobulin determinations were performed. Four infants were infected. HIV isolation, HIV p24 antigen and polymerase chain reaction were positive within 3 months in all infected infants (100% sensitivity). False positive rates for a single test were 18, 9 and 9%, respectively. Median age of clearance of maternal antibodies was 13.4 +/- 2.1 months. Serum immunoglobulin G was significantly elevated after 6 months in all 4 infected infants. Advanced maternal age (> or = 30 years; Fisher's exact test, P > 0.014) was associated with transmission. A trend in higher maternal viral burden was observed among transmitters. Non-syncytium-inducing phenotype was present initially in all transmitting mothers.

Analysis of Variance↗
PubMed1994

HLA non-identical T-cell-depleted bone marrow transplantation for primary immunodeficiency diseases.

BACKGROUND: Bone marrow transplantation (BMT) is usually the only procedure offering cure for children with life-threatening immune deficiency disorders, but compatible sibling donors are frequently unavailable. AIMS AND METHODS: To examine the outcome of HLA non-identical T-cell-depleted BMT carried out between April 1985 and May 1992 in 11 patients with primary immunodeficiency diseases and to seek prognostic factors. RESULTS: Eight patients achieved sustained engraftment, one after a second BMT. One further patient engrafted transiently, but rejected the graft five months later. Acute graft-versus-host disease (GVHD) grade II was seen in one and chronic GVHD was seen in three children. Seven patients survived beyond six months, six with donor T cell and five with donor B cell engraftment. At present, five patients (46%) are alive with immune reconstitution at a median follow-up of 14 months (range 6 to 78 months). The major factor associated with outcome was the presence of any infection within one week of BMT (p = 0.01). The presence of lung infection also tended to be a poor prognostic factor (p = 0.06) but did not reach significance, presumably because of the small sample size. HLA non-identical (parental) T-cell depleted BMT plays an important role in the cure of children with immunodeficiencies who do not have an identical sibling donor. Survival can be further improved if the diagnosis of immunodeficiency disease is made early and BMT undertaken before significant infections occur. CONCLUSIONS: The availability of T-cell depleted haploidentical parental bone marrow transplant can be anticipated to improve outcome significantly for children with severe immunodeficiency, especially when diagnosed early.

Bone Marrow Transplantation↗
PubMed1994

Age-related response to lidocaine-prilocaine (EMLA) emulsion and effect of music distraction on the pain of intravenous cannulation.

OBJECTIVE: To compare the efficacy of a local anesthetic cream and music distraction in reducing or preventing pain from needle puncture (intravenous cannulation) in children. A secondary aim was to examine the influence of age on the pain report and behavior and on the therapeutic outcome. METHODOLOGY: Children aged 4 to 16 years (N = 180) who were to undergo surgery under general anesthesia via intravenous cannulation were randomly allocated to one of three interventions. The comparison of lidocaine-prilocaine emulsion (EMLA, Astra) and a placebo emulsion was double-blind. Stratification by age group (4 to 6, 7 to 11, 12 to 16) ensured an equal number of children (20) in each intervention/age group category. A global assessment of the behavioral reaction to the procedure was made by the principal investigator, taking into account vocal, verbal, facial, and motor responses. The child was asked to assess pain severity on the Faces Pain Scale (FPS) and a visual analogue toy (VAT). The scales were applied conservatively as ordinal scales: FPS 0 to 6; VAT 0 to 10. RESULTS: Children who received lidocaine-prilocaine emulsion reported less pain (mean FPS score = 1.42) compared with placebo emulsion (mean FPS score = 2.58) and with music distraction (mean FPS = 2.62). There was a highly significant therapeutic effect (P < .001) on the self-report and behavioral scores. Younger children, regardless of intervention, reported significantly more pain than the older children (mean FPS scores: 2.85, 2.33, 1.43 for age groups 4 to 6, 7 to 11, and 12 to 16 respectively; P < .001). The superiority of the local anesthetic emulsion was maximal in the youngest age group (4 to 6) almost eliminating pain-related behavior, and multiple regression analysis confirmed significant age and treatment effects and revealed interaction between therapeutic effect and age. Although a trend favoring the active emulsion was evident in the older children (7 to 11, 12 to 16) the differences were not significant. The pain scores were influenced by the type (gauge) of cannula, but this did not affect the conclusion regarding therapeutic and age effects. There was no influence of sex, experience with venipuncture, or whether the child was anxious on arrival in the operating room. CONCLUSIONS: The results show that lidocaine-prilocaine emulsion is highly effective in preventing pain from venipunctures in young children, the group in most need of prevention.

Adolescent↗
PubMed1993

HIV infection in paediatric practice.

Worldwide, most new HIV infections in children are transmitted from the mother before, during or after birth. This mode of transmission is likely to become more common in Australian paediatric practice, sometimes in circumstances where the mother's HIV status is unknown and unsuspected.

AIDS-Related Opportunistic Infections↗
PubMed1993

Breast-feeding during primary maternal human immunodeficiency virus infection and risk of transmission from mother to infant.

Examination of breast-fed infants of the complete cohort of Australian women whose primary human immunodeficiency virus (HIV) infection occurred postpartum allows for an estimate of risk of transmission of HIV. Ten women with no other risk factors were infected via blood transfusion postpartum. They breast-fed for up to 9 months; 2 of their infants were infected. Another woman, who shared needles for intravenous drug use, seroconverted 6-10 months post-partum. She breast-fed for 14 months. Retrovirus was visualized in the cellular and cell-free fraction of her milk by electron microscopy. Infection in her infant was confirmed at 12 months. Thus, 3 of the 11 babies at risk became infected, providing an estimate of risk of 27% for breast-feeding during primary maternal infection (95% confidence interval, 6-61%). These data establish the association of primary maternal HIV infection and breast-feeding with a high risk of transmission to infants.

Animals↗
PubMed1993

Medicinal chemistry of gold.

In order to determine the mechanism of action of the anti-arthritic gold complexes, it is necessary to understand the physicochemical properties of these complexes and the exchange of ligands which may occur under physiological conditions, since these factors control the cellular uptake and effects of the gold complexes. Present leads to the forms of gold which may be taken up by cells include the metabolism of the injectable complexes to aurocyanide which is quite a potent inhibitor of the oxidative burst of neutrophils and an even more potent inhibitor of the proliferation of lymphocytes. Further metabolism of aurocyanide to Au(III) complexes is also possible. The orally active complex, auranofin, is active in various cellular systems but the relevance of its in vitro actions to its clinical effects is not known, in part, due to its unknown metabolism. A potentially active derivative of auranofin is a presumed metabolite which can be transferred from plasma to red blood cells. If this metabolite is taken up by red blood cells, then it may be taken up by target cells with consequent pharmacological activity.

Antirheumatic Agents↗
PubMed1993

Pediatric HIV: Australian perspective.

Pediatric infection with human immunodeficiency virus (HIV) in Australia, as elsewhere, now reflects HIV seroprevalence in women of childbearing age although numbers remain small. A perinatal transmission rate of approximately 30% has been observed. The rate appears to be higher for breast-fed babies; exclusively bottle-fed babies of HIV-infected mothers appear to have a risk of < 20% of acquiring HIV perinatally. Although the seroprevalence rate in women of childbearing age in Australia remains low, routine antenatal screening will not be cost-effective. Although passively acquired maternal antibody may confound serodiagnosis for up to 18 months, in practice, HIV infection, when present, can be detected clinically or with use of other laboratory parameters (p24, polymerase chain reaction, viral culture, hyperglobulinemia) during the first 6 months of life. Zidovudine appears to be relatively nontoxic in children and effective in producing weight gain and preventing opportunistic infection. Although experience with didanosine is limited, this drug appears to have a very acceptable toxicity profile and the advantage of twice-daily dosing. However, the bioavailability and penetration into the cerebrospinal fluid are poor. Neurological disease can improve when absorption is adequate. Residential family camps may help to reduce isolation for families and provide them with an opportunity for improving their understanding of HIV through interaction with peers and professionals.

Adult↗
PubMed1992

Gold complexes and activation of human polymorphonuclear leukocytes. Dissociation of changes in membrane potential and oxidative burst.

The effects of the gold compounds on the alteration of membrane potential of polymorphonuclear leukocytes (PMN) in response to various stimulants have been compared with their effects on the oxidative burst. The present studies have shown that gold complexes [auranofin (AF), aurothiomalate (Autm), aurocyanide (Au(CN)2-)] have contrasting effects on the membrane potential of 3,3'-dipentyloxacarbocyanine [di-O-C5(3)] loaded PMN. Au(CN)2- at concentrations which inhibit the oxidative burst of PMN did not affect the membrane depolarization after activation of PMN by phorbol myristate acetate (PMA) and N-formyl-methionyl-leucyl phenylalanine (FMLP); Autm slightly stimulated the oxidative burst but had no effect on the depolarization of PMN. In contrast, AF inhibited the depolarization of stimulated PMN to an extent depending upon the concentration of AF, the time of preincubation and the stimulus. The membrane depolarization of PMN caused by PMA, FMLP and concanavalin A (ConA) was inhibited by AF (5 microM) but the depolarization induced by calcium ionophore (A23187) was not affected. AF at the same conditions inhibits the oxidative burst of PMN induced by all these single stimuli including the calcium ionophore. Dissociation of membrane depolarization and superoxide generation caused by AF was also seen in PMN activated by two stimuli. AF (5 microM) had little initial inhibitory effect on the oxidative burst of PMN stimulated by combinations of PMA and ConA or PMA and FMLP whereas it almost totally blocked the depolarization caused by these combinations. Preincubation of cells with 5 microM AF for less than 5 min prior to the addition of PMA allowed membrane depolarization which was followed rapidly by repolarization. None of the gold complexes studied had any effect on the resting membrane potential of PMN.

Auranofin↗
PubMed1992

Report on the X-linked lymphoproliferative disease in an Australian family.

X-linked lymphoproliferative disease is characterized by immune deficiency, particularly to the Epstein-Barr virus and by a tendency to develop fatal infectious mononucleosis, acquired hypogammaglobulinaemia or malignant lymphoma. This disorder has been diagnosed in three boys, two brothers and a maternally related cousin, residing in Australia. The proband presented at 6 years of age with fulminating infectious mononucleosis. His 9 year old male cousin had developed an ileal Burkitt lymphoma one year earlier. Immunological and molecular genetic evidence is presented to support our view that his younger sibling is also affected with this condition. DNA linkage studies using probes to DXS10 and DXS37 provide confirmatory evidence for the diagnosis in the proband's brother and information on carrier status in female family members.

Agammaglobulinemia↗
PubMed1992

Failure of allogeneic bone marrow transplantation to benefit HIV infection.

A 16 year old boy underwent allogeneic bone marrow transplantation (BMT) from an human leukocyte antigen (HLA)-identical sibling for severe aplastic anaemia. He was symptomatic for 7 years before transplantation and had received multiple red blood cell and platelet transfusions. Conditioning for BMT consisted of cyclophosphamide, antilymphocyte globulin and total lymphoid irradiation. Engraftment was rapid, there was no evidence of rejection despite the history of multiple blood product transfusions and he did not develop acute or chronic graft versus host disease. He was well for the first 8 months after transplantation but then developed fevers, interstitial pneumonia, herpes simplex infections and cytomegalovirus enteritis. Serological studies revealed antibodies to human immunodeficiency virus (HIV) and he was considered to have acquired immune deficiency syndrome (AIDS). Retrospective analysis of the serum samples showed that he was seronegative for HIV until approximately 10 months before transplantation when his serum became HIV positive. Lymphocyte function studies done after transplantation suggested immunologic recovery at 3 months post-transplant with a brisk though subnormal response to phytohaemagglutinin stimulation. T cell subset analysis performed subsequently showed complete absence of CD4 positive cells indicating immune incompetence which was associated with clinical features of AIDS. Bone marrow transplantation had failed to produce sustained immunologic reconstitution and prevent the progression of HIV to which he ultimately succumbed.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Searches for matched and closely matched related and unrelated bone marrow donors undertaken in a single paediatric unit.

Information regarding the likelihood of finding suitable marrow donors is limited. In order to determine this potential, all patients who received their primary care at a single paediatric institution over a 9 year period and in whom tissue typing studies were initiated are reviewed. Forty-five (31.3%) of 144 patients had a sibling who was human leucocyte antigen (HLA) identical. A further 16 (11.2%) patients had immediate or more distant relatives who were either HLA identical (2.7%) or matched for five of six HLA antigens (8.3%). The possibility that a parent was closely matched with the patient was suggestive from the typing of siblings alone in only half the cases. Unrelated HLA matched donors were identified in four (27%) of 17 bone marrow bank searches. Overall, a potential related donor was identified within the family for 42% of patients and this figure rose to 45% when successful marrow bank searches were included. It can be concluded that initial typing should include both the parents and siblings. If a suitable donor is not found then an extended family and/or bone marrow bank search will identify additional suitable donors in a significant number of families.

Bone Marrow Transplantation↗
PubMed1991

Auranofin inhibits the activation pathways of polymorphonuclear leukocytes at multiple sites.

In order to characterize the mechanism by which the anti-rheumatic gold complex auranofin (AF) affects the functions of resting and activated polymorphonuclear leukocytes (PMN) the following studies were performed: (1) The effect of AF on the major processes involved in the respiratory burst of PMN: glucose transport and phosphorylation; hexose monophosphate (HMP) shunt activity in intact cells and in a cell-free system; superoxide production by particulate fractions and intact PMN measured as lucigenin-dependent chemiluminescence. (2) A comparison of the effects of AF added to the PMN before, at the time of, or subsequent to the stimulants [N-formyl-methionyl-leucyl phenylalanine (FMLP), concanavalin A (ConA), calcium ionophore (A23187) and phorbol myristate acetate (PMA)]. (3) The effect of AF on PMN activated by two stimulates (PMA, ConA) added sequentially. AF (0.1-10 microM) caused a dose-dependent inhibition of lucigenin-dependent chemiluminescence regardless of the activator (FMLP, ConA, A23187, PMA) when AF was added before the activator. In contrast, when AF was added to PMN after stimulation, it inhibited only the chemiluminescence of PMN stimulated by PMA. Furthermore, the chemiluminescence was largely unaffected by AF in sequentially activated PMN. The relative sensitivity to AF of the various processes studied indicates that blockade of the activation signal appears to be responsible for inhibition of the respiratory burst of PMN.

Auranofin↗