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Biomedical subjects

P Palmer

Publications and source records attributed to P Palmer.

At least 19 recordsLinked to original sources
PubMed2004

Ninety-six-week efficacy of combination therapy with lamivudine and tenofovir in patients coinfected with HIV-1 and wild-type hepatitis B virus.

We describe 6 patients who were coinfected with human immunodeficiency virus (HIV) type 1 and wild-type hepatitis B virus (HBV), in whom complete and sustained antiviral activity against wild-type HBV strains was attained during 96 weeks of combination therapy with lamivudine and tenofovir. The use of combination therapy with lamivudine and tenofovir for the treatment of HBV infection is very promising in the treatment of HIV/HBV coinfection.

Adenine↗
PubMed2004

HIV seroprevalence, uptake of interventions to reduce mother-to-child transmission and birth outcomes in greater Kingston, Jamaica.

BACKGROUND: The seroprevalence of HIV among pregnant women in the Caribbean is 2-3% and increasing. The Kingston Paediatric and Perinatal HIV Programme is developing and implementing a unified programme to eliminate mother-to-child transmission (MTCT) of HIV in Kingston, Jamaica. METHODS: Pregnant women presenting to Kingston Metropolitan Antenatal Clinics, Victoria Jubilee Hospital, Spanish Town Hospital and the University Hospital of the West Indies had HIV serology performed by ELISA, or by the new Determine Rapid Test after receiving group counselling. HIV-positive women were referred to High Risk Antenatal Clinics. Antiretroviral prophylaxis with zidovudine (AZT), or nevirapine was given. Care was administered using a standard protocol by a multi-disciplinary team of public and academic healthcare personnel. RESULTS: In year one, 19,414 women delivered Among 14,054 women who started antenatal care for this period, 5,558 (40%) received group counselling and 7,383 (53%) received HIV-testing. During the fourth quarter of follow-up, these comparative rates were 66% (2049/3 118) and 72% (2260/3118) respectively. HIV seroprevalence overall was 2.1% (152/7 383). One hundred and seven HIV+ women at varying gestational ages were identified in the programme, 72 had so far received AZT and nine nevirapine (76%). 0f 84 deliveries, birth outcomes were 75 live births (89%), six neonatal deaths and four maternal deaths (all from HIV/AIDS). Major challenges include repeat pregnancies of 36% despite prior knowledge of HIV seropositivity and poor partner notification with only 30% (32) having a HIV-test. Although rates of HIV testing in pregnant women in Greater Kingston are increasing, rates of testing overall remain sub-optimal. On the labour ward, there was sub-optimal identification of the HIV+ pregnant woman and administration of AZT chemoprophylaxis, along with issues of patient confidentiality and stigma. CONCLUSION: This programme needs strengthening in order to reduce maternal-fetal transmission of HIV in Greater Kingston, Jamaica "pMTCT-PLUS, or comprehensive family-centred care, is the next step".

Adolescent↗
PubMed2004

Socio-demographic characteristics of HIV-exposed and HIV-infected Jamaican children.

BACKGROUND: In the face of the continuing pandemic of HIV/AIDS, the burden of the disease is now largest in the resource-poor developing world. The Joint United Nations Programme on HIV/AIDS (UNAIDS) has listed the adult prevalence rate for the Caribbean as second only to Sub-Saharan Africa. OBJECTIVE: To document the socio-demographic characteristics of paediatric and perinatal HIV/AIDS in Kingston, Jamaica. METHODS: A cohort of HIV-infected pregnant women were identified at the leading maternity centres in Kingston and St Catherine and were enrolled in the Kingston Paediatric and Perinatal HIV/AIDS Programme. Infants born to mothers within the programme were prospectively enrolled. Infants and children identified after delivery, whether HIV-exposed or infected, were also enrolled (retrospective group). All were followed according to standardized protocols. RESULTS: We report on a total of 239 children, 78 (prospective group) and 161 (retrospective group). Among the retrospective group, 68% were classified as infected. For the prospective group, the patients were recruited within twenty-four hours of birth in 98.7% of cases, whereas in the retrospective group, the median age of recruitment was 2.6 years. The median age of the mother was 27 years and that of the father was 33 years. There were seven teenage mothers. Twenty-six per cent of the children were in institutional care. Family size ranged from one to nine children--the median was two children. For those parents where occupation was reported, the majority held semi-skilled or unskilled jobs. Patients attended their regional clinics. CONCLUSION: HIV/AIDS represents a significant human and financial burden on a developing country such as Jamaica and this underscores the need for urgent and sustained interventions to stem the epidemic.

Child, Preschool↗
PubMed2004

Uptake of interventions, outcomes and challenges in caring for HIV-exposed infants in Kingston, Jamaica.

BACKGROUND: In a few Caribbean islands, prevention of mother-to-child transmission (pMTCT) of HIV with zidovudine prophylaxis has reduced transmission rates from 27 - 44% to 5.5 - 9 %. OBJECTIVES: To highlight the uptake of interventions, preliminary outcomes and challenges in caring for HIV-exposed infants in a pMTCT HIVprogramme in a resource-limited setting. METHOD: A cohort of HIV-infected pregnant women were identified at the leading maternity centres in Greater Kingston through HIV counselling and testing and enrolled in the Kingston Paediatric and Perinatal HIV/AIDS Programme. Antiretroviralprophylaxis with zidovudine or nevirapine was given to the HIV-positive women and their newborns along with formula feeding. Some infants were enrolled retrospectively and followed irrespective of whether they had or had not received antiretroviral prophylaxis. A multidisciplinary team at the paediatric centres supervised protocol-driven management of the infants. Infants were followed for clinical progress and definitive HIV-infection status was to be confirmed at 18 months of age by ELISA or the Determine Rapid Test. RESULTS: During September 1, 2002 through August 31, 2003, 132 HIV-exposed infants were identified. For those infants prospectively enrolled (78), 97% received antiretroviral prophylaxis and 90% were not breastfed For all HIV-exposed children, 90% received cotrimoxazole prophylaxis and 88% continued follow-up care. Ninety-two per cent of all the infants remained asymptomatic and five died; of these deaths one is possibly HIV-related (severe sepsis at 11 weeks). This infant was retrospectively identified, had received no antiretroviral prophylaxis and was breastfed The main programme challenges, which were overcome, included the impact of stigma, compliance with antiretroviral chemoprophylaxis, breast-milk substitution and follow-up care. Financial constraints and laboratory quality assurance issues limited early diagnosis of HIV infection. CONCLUSION: Despite the challenges, the expected outcome is to prevent 50 new cases of HIV/AIDS in children living in Greater Kingston per year (300 over six years).

Antibiotic Prophylaxis↗
PubMed2004

CDC-defined diseases and opportunistic infections in Jamaican children with HIV/AIDS.

OBJECTIVE: To document the frequency of Centers for Disease Control and Prevention (CDC)-defined clinical conditions, opportunistic and co-infections among children with HIV/AIDS. METHODS: This prospective, observational study reports the findings of 110 HIV-infected children followed in multicentre ambulatory clinics during September 1, 2002, to August 31, 2003, from the 239 children enrolled in the Kingston Paediatric and Perinatal HIV/AIDS Programme, Jamaica. We describe the clinico-pathologic characteristics of these children with HIV/AIDS, using the CDC criteria. RESULTS: The client distribution by clinic site was as follows: the University Hospital of the West Indies, 71 (64.6%), Bustamante Hospital for Children, 23 (20.9%), Comprehensive Health Centre 13 (11.8/%) and Spanish Town Hospital, 3 (2.7%). The median age of the 110 children with HIV/AIDS was 6.0 years (range 0.9-17.5). Mode of transmission was primarily mother-to-child (88.0%) and only 4% maternal/infant pairs received antiretroviralprophylaxis. Grouped by CDC category: 17 (15.4%) were asymptomatic (N), 22 (20.0%) mildly symptomatic (A), 30 (27.3%) moderately symptomatic (B) and 41 (37.3%) severely symptomatic (C). The most common CDC-defining symptoms were lymphadenopathy (12, 42.8%) and asymptomatic (6, 21.4%) in category N; lymphadenopathy (30, 29.7%), dermatitis (20, 19.8%) and persistent or recurrent upper respiratory tract infections (20, 19.8%) in category A; bacterial sepsis (18, 34.6%) and recurrent diarrhoea (11, 21.2%) in category B; and wasting (28, 30.0%), encephalopathy (26, 27.9%), and serious bacterial infections (15, 16.1%) in category C; Pulmonary tuberculosis (7, 7.5%) and Pneumocystis (jiroveci) carinii pneumonia; (5, 5.4%) were the most frequent opportunistic infections. Streptococcus pneumoniae (10, 30.3%) was the most common invasive bacterial pathogen causing sepsis and Escherichia coli (14, 34.2%) was the most common bacterial pathogen causing urinary tract infections, among the cohort. Thirty-three per cent commenced antiretroviral drugs (ARVs). There were 57 hospitalizations and five deaths. CONCLUSIONS: The study is an important step toward documentation of the natural history of paediatric HIV/AIDS in a primarily ARV-naive population from a developing country. It promotes training in paediatric HIV management as we move toward affordable access to antiretroviral agents in the wider Caribbean and the implementation of clinical trials.

AIDS-Related Opportunistic Infections↗
PubMed2001

Congenital HCMV infection: a collaborative and comparative study of virus detection in amniotic fluid by culture and by PCR.

Cytomegalovirus (HCMV) infection is the leading cause of congenital virus infection in developed countries, affecting an estimated 1% of births. This antenatal infection can cause serious sequelae. Strategies for prevention and treatment must, therefore, be agreed upon, entailing a preliminary performance assessment of antenatal virus diagnosis techniques. Between 1992 and 1999, HCMV serology status was established for 19456 pregnant women in four French hospitals. Seronegative patients (55.4%) were given serology screening, and antenatal diagnosis was given to 152 women who had shown seroconversion during their pregnancies (1.4%). The detection of HCMV transmission from mother to fetus was finally established in 95 cases, using polymerase chain reaction (PCR) and viral culture methods for detecting HCMV in the amniotic fluid. These results were compared with viral culture of children's urine after birth, enabling us to distinguish between children really infected in utero (30%) and non-infected children (70%). The results of the virus culture and those of PCR were identical in 94 of the 95 cases, with one discrepancy (culture-/PCR+). The two diagnosis techniques had identical sensitivity (72%), with culture proving slightly more specific than PCR (98.4% as opposed to 96.9%). Positive prediction values for culture and for PCR were, respectively, 95.6 and 91.3%. Antenatal virus diagnosis on amniotic fluid was negative with both techniques in 8 out of 29 cases of children born with HCMV infection (VPN=89%). Over half of these wrongly negative results can be explained by amniocentesis carried out too early in the pregnancy or too early with respect to the mother's primary infection.

Amniotic Fluid↗
PubMed2001

CAMPATH-1M T-cell depleted BMT for SCID: long-term follow-up of 19 children treated 1987-98 in a single center.

BACKGROUND: SCID can be cured by BMT. Depletion of mature T cells from BM has enabled HLA non-identical stem-cell transplantation. We report the outcome of 30 patients treated with 37 T-cell depleted BMT procedures using CAMPATH-1M in vitro between 1987-98 in a single center. METHODS: Immune reconstitution and quality-of-life were assessed in 19 longterm survivors. All but two received pre-transplant conditioning. T- and B-cell chimerism, numbers and function were analyzed during a median follow-up of 5.3 years (range 1.33-12). RESULTS: The overall engraftment rate was 59%, six children required repeated BMT and the survival rate was 63%. All have donor T cells, 58% normal T-cell numbers and 74% normal T-cell function. Of 17 evaluated, 16 patients (94%) have normal IgM and IgG levels, and production of specific Abs to protein Ags, but only 5/16 (31%) have a good response to pneumococcal polysaccharide. Early and late post-BMT complications were rare and there were no delayed deaths. Only one child continues on long-term i.v. Ig 4-years post-BMT. Eleven children died (37%). DISCUSSION: CAMPATH-1M T-cell depleted BMT for SCID resulted in 63% survival. Deaths of 11 children were mainly due to pre-existing infections. Seventeen of 19 long-term survivors have normal immune function and good quality-of-life.

Alemtuzumab↗
PubMed2001

Relationship between infant sleep position and motor development in preterm infants.

To determine whether motor development in premature infants varies according to sleep position, we evaluated 213 infants <1750 g birth weight enrolled in the Collaborative Home Infant Monitoring Evaluation (CHIME). At 56 weeks postconceptional age (PCA), sleep position was determined by maternal report, and the Bayley Scales of Infant Development 2nd Edition (BSID-II) were performed. Infants who slept supine were less likely than infants who slept prone to receive credit for maintaining the head elevated to 45 degrees (p = .021), and infants who slept nonprone were less likely than prone sleepers to receive credit for maintaining the head elevated to 90 degrees and lowering with control (p = .001). The Psychomotor and Mental Development Indices at 56 and 92 weeks PCA were not altered by usual sleep position at 56 weeks PCA. In summary, infants sleeping supine are less able to lift the head and lower with control at 56 weeks PCA, but global developmental status was unaffected. Supine sleeping has been associated with decreased risk for sudden infant death syndrome, but compensatory strategies while awake may be needed to avoid delayed acquisition of head control.

Child Development↗
PubMed2000

Antibody-dependent induction of type I interferons by poliovirus in human mononuclear blood cells requires the type II fcgamma receptor (CD32).

The induction of type I interferons (IFNs) in peripheral blood mononuclear cells (PBMCs) can be triggered by viral infection or exposure to viral glycoproteins. Here we show that the IFN-alpha-inducing capacity of attenuated poliovirus vaccine strains is dramatically enhanced in the presence of human polyvalent immunoglobulin G (IgG). The transcription of both IFN-alpha and IFN-beta genes was detected by RT-PCR in stimulated cells. This antibody-dependent activation of type I IFNs genes was also observed with Formalin-inactivated or UV-inactivated poliovirus, but not with empty poliovirus capsids. The ability of poliovirus-antibody complexes to induce IFN-alpha was specifically inhibited when PBMCs were preincubated with an excess of the Fc fragment of IgG. Monoclonal antibodies directed to FcgammaRII (CD32) were also inhibitory, whereas antibodies to the two other classes of Fcgamma receptors, CD16 and CD64, were not. Also, aggregation of FcgammaRII by anti-CD32 antibodies alone failed to induce IFN-alpha production. Our results suggest that induction of type I interferons by poliovirus-antibody complexes depends on CD32-mediated phagocytosis of RNA-containing viral particles. As suggested by the results of an ELISPOT analysis, only a fraction of the IFN-alpha-producing cells are able to synthesize IFN-alpha in response to poliovirus-IgG complexes.

Antibodies, Viral↗
PubMed2000

EORTC 10941: A phase II study of liarozole in postmenopausal patients with 'chemotherapy-resistant' or 'potentially hormone sensitive' metastatic breast cancer.

Liarozole is an imidazole compound that inhibits enzymes involved in steroid hormone aromatisation and retinoid metabolism. The IDBBC branch of the EORTC has performed a series of phase II studies of the agent in four groups of postmenopausal women with metastatic breast cancer. This paper reports the results of the first two groups: 'Chemotherapy Resistant' (unrestricted ER status, 1 or 2 prior chemotherapy regimens, 0-2 prior hormonal therapies) and 'Potentially Hormone Sensitive' (ER positive or unknown, 1 or 2 prior hormonal therapies with a substantial disease free interval or progression free survival, and no history of chemotherapy for metastatic disease). Liarozole was administered at 150-300 mg orally bid. The objective response rate was 12% in the 'Chemotherapy Resistant' group (n = 34), and 22% in the 'Potentially Hormone Sensitive' group (n = 37), with median response durations of 9 and 14 months, respectively. Median time to treatment failure was only 2 months in both groups, due largely to the significant percentage (24%) of patients who ceased treatment following excessive mucocutaneous and gastrointestinal toxicity. This adverse event profile will limit its use in breast cancer. Results of the 'ER negative' and 'Tamoxifen Refractory' groups will be reported in a future paper.

Adult↗
PubMed2000

A sedation technique for implant and periodontal surgery.

OBJECTIVE: Evaluation of a sedation technique which involved titrating intravenous midazolam to an 'ideal' sedation end point, followed by a continuous infusion of propofol. This technique might be a satisfactory alternative to general anaesthesia for implant surgery in anxious patients or when procedures exceed 60-min duration. MATERIAL AND METHODS: 20 patients were treated on 23 occasions. A 2-mg bolus of midazolam was injected intravenously followed after 90 s by 1 mg increments until the patient was adequately sedated. 30 min after this induction with midazolam, a propofol infusion was started at a rate which varied between 0-300 mg/h (0-30 ml/h). The actual infusion rate was adjusted in order to maintain the optimum sedation level which had been achieved using midazolam. The quality of sedation was assessed using Ellis and Sedation scores. RESULTS: Midazolam dosage varied between 5 and 14 mg. The initial propofol infusion rate was 200 mg/h (20 ml/h) for 21 of the 23 implant surgery treatments. CONCLUSION: The sedation technique described takes advantage of the differing pharmacokinetic properties of midazolam and propofol. Initial sedation was achieved using midazolam, this was then maintained using a variable propofol infusion. The shorter distribution and elimination half-lifes of the latter drug made matching the level of sedation to the patient's needs easier and also provided good short-term recovery.

Adult↗
PubMed2000

No evidence of measles virus in stapes samples from patients with otosclerosis.

Otosclerosis is a localized bone dystrophy of unknown etiology mainly involving the stapes. The hypothesis of a persistent infection by the measles virus was based on the inconstant detection of the virus by various methods, including reverse transcription-PCR (RT-PCR) of patients' stapes samples. The aim of this work was to investigate the presence of the measles virus in stapedial otosclerosis foci by different sensitive methods. Pathologic stapes samples were obtained from 35 patients suffering from otosclerosis. Measles virus detection was performed by (i) cocultures of Vero cells and primary cell cultures of bone samples (n = 7), (ii) immunofluorescence study of these cocultures (n = 3), and (iii) RT-PCR on RNA directly obtained from fresh frozen samples (n = 28) and on RNA extracted from the primary cell cultures (n = 2). Viral genomic regions coding for N (nucleoprotein) and M (matrix) proteins were separately amplified. PCR sensitivity was optimized on the measles virus Edmonston strain. Glyceraldehyde-3-phosphate dehydrogenase mRNA was used as a marker of total RNA recovery. PCR products were tested by Southern blot hybridization technique to improve sensitivity and specificity. PCRs amplifying the M and the N protein genes were able to detect the control measles virus RNA at titers as low as 0.1 and 0.01 50% tissue culture infective dose, respectively. With these highly sensitive methods, we could not evidence the presence of the measles virus in any of our bone samples or primary bone cell cultures. Our results do not confirm the hypothesis of persistent measles virus infection in otosclerosis.

Adult↗
PubMed2000

Identification of mature and immature human thymic dendritic cells that differentially express HLA-DR and interleukin-3 receptor in vivo.

We have previously shown that thymic CD34+ cells have a very limited myeloid differentiation capacity and differentiate in vitro mostly into CD1a+-derived but not CD14+-derived dendritic cells (DC). Herein we characterized the human neonatal thymic DC extracted from the organ in relationship with the DC generated from CD34+ cells in situ. We show that in vivo thymic DC express E cadherin, CLA, CD4, CD38, CD40, CD44, and granulocyte-macrophage colony-stimulating factor-R (GM-CSF-R; CD116) but no CD1a. According to their morphology, functions, and surface staining they could be separated into two distinct subpopulations: mature HLA-DRhi, mostly interleukin-3-R (CD123)-negative cells, associated with thymocytes, some apoptotic, and expressed myeloid and activation markers but no lymphoid markers. In contrast, immature HLA-DR+ CD123hi CD36+ cells with monocytoid morphology lacked activation and myeloid antigens but expressed lymphoid antigens. The latter express pTalpha mRNA, which is also found in CD34+ thymocytes and in blood CD123hi DC further linking this subset to lymphoid DC. However, the DC generated from CD34+ thymic progenitors under standard conditions were pTalpha-negative. Thymic lymphoid DC showed similar phenotype and cytokine production profile as blood/tonsillar lymphoid DC but responded to GM-CSF, and at variance with them produced no or little type I interferon upon infection with viruses and did not induce a strict polarization of naive T cells into TH2 cells. Their function in the thymus remains therefore to be elucidated.

Antigens, CD↗