Outcome of HIV-infected Pregnant Women and Their Offspring in Barbados: A Five-year Study.

OBJECTIVES: To describe the outcome of HIV-infected pregnant women and their offspring during a five-year period. METHODS: The medical records of HIV-infected pregnant women who delivered between January 2007 and December 2011 and their HIV-exposed infants were reviewed. Demographics, outcome of pregnancy and infants, and clinic attendance were analysed. Data were entered on a Microsoft Excel spreadsheet. RESULTS: One hundred and forty-three women, aged 17-45 years (mean 27.3 years), were included in the study with 143 pregnancies and 142 pregnancy outcomes being recorded. One woman migrated before delivery. There were 122 live births and 18 (13%) terminations: 13 (9%) elective and five (4%) spontaneous. There was one ectopic pregnancy and one stillbirth. One hundred and twenty-two (85%) women were unmarried. Women were prescribed highly active antiretroviral therapy for prevention of mother-to-child transmission from the time of booking, apart from those opting for terminations or those who had spontaneous abortions. For clinic follow-up, 105 (73%) had regular attendance, 30 (21%) defaulted and could not be located despite intense tracking, four attended irregularly, and one refused to attend clinic. Four (3%) migrated after delivery. Two (1%) mothers died during the period of study. Two successive DNA polymerase chain reaction tests done within four months of age did not substantiate any cases of infant infection. CONCLUSION: This study revealed that there was a good outcome and compliance with follow-up of HIV-infected pregnant women and their offspring.

Diagnostic value of sentinel lymph node biopsy in head and neck cancer: a meta-analysis.

This study aimed to evaluate the diagnostic reliability of sentinel lymph node biopsy in patients with squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, and larynx by reviewing the published literature. A systematic literature review was performed using MEDLINE from 1970 to 2011. With Boolean search strings, search terms included sentinel node, supraglottic, supraglottis, tongue, head and neck, oral, pharynx, laryngeal, and larynx. Additional studies were identified through article references. Duplicate data and articles were excluded based on treating institution and study inclusion time period. Additional studies were excluded if the head and neck subsite or tumor stage was not specifically identified or if the sentinel lymph node biopsy occurred in previously treated necks. All patients had sentinel lymph node biopsy performed followed by a concurrent neck dissection. Twenty-six studies met our inclusion criteria (n = 766 patients). The pooled sensitivity and negative predictive value of SLNB for all head and neck tumors was 95 % (95 % CI 91-99 %) and 96 % (95 %CI 94-99 %), respectively. The overall sensitivity and negative predictive value of SLNB in the subset of oral cavity tumors (n = 631) was 94 % (95 % CI 89-98 %) and 96 % (95 % CI 93-99 %), respectively. One-hundred percent of oropharyngeal (n = 72), hypopharyngeal (n = 5), and laryngeal (n = 58) tumor sentinel lymph biopsy results correlated with subsequent neck dissections giving a negative predictive value of 100 %, showing that, sentinel lymph node biopsy is a valid diagnostic technique to correctly stage regional metastases in patients with head and neck squamous cell carcinoma.

Apricoxib upregulates 15-PGDH and PGT in tobacco-related epithelial malignancies.

BACKGROUND: Despite focused research in conventional therapies and considerable advances in the understanding of the molecular carcinogenesis of head and neck squamous cell carcinoma (HNSCC), the 5-year survival rate for patients with advanced disease remains ∼15-20%. The major causes of HNSCC-related deaths are cervical node and distant metastasis. E-cadherin has a key role in epithelial intercellular adhesion and its downregulation is a hallmark of epithelial-mesenchymal transition (EMT), which is associated with invasion, metastasis, and poor prognosis. Epithelial-mesenchymal transition is the major mechanism responsible for mediating invasiveness and metastasis of epithelial cancers. Recently, we reported the role of E-cadherin transcriptional repressors in the inflammation-induced promotion of EMT in HNSCC, which is mediated by COX-2. These findings suggest that therapies targeting the cyclooxygenase pathway may diminish the propensity for tumour metastasis in HNSCC by blocking the PGE2-mediated induction of E-cadherin transcriptional repressors. METHODS: Herein, we evaluate the efficacy of the COX-2 inhibitor, apricoxib, in HNSCC cell lines. Apricoxib is effective in preventing tumour cell growth in three-dimensional, and anchorage-independent growth assays, as well as decreasing the capacity for tumour cell migration. RESULTS: Herein, we evaluate the efficacy of the COX-2 inhibitor, apricoxib, in HNSCC cell lines. Apricoxib is effective in preventing tumour cell growth in three-dimensional, and anchorage-independent growth assays, as well as decreasing the capacity for tumour cell migration. Treatment of HNSCC cells with apricoxib also causes greater upregulation of E-cadherin and Muc1 expression and downregulation of vimentin, as compared with celecoxib treatment. This has significant implications for targeted chemoprevention and anti-cancer therapy because E-cadherin expression has been implicated as a marker of sensitivity to epidermal growth factor receptor tyrosine kinase inhibitor and other therapies. We show for the first time the molecular mechanisms underlying the efficacy of apricoxib in HNSCC cells. CONCLUSION: In addition to reversing EMT via inhibition of COX-2, apricoxib upregulates 15-prostaglandin dehydrogenase and the prostaglandin transporter, thereby reducing the levels of active PGE2 by both suppressing its synthesis and increasing its catabolism. These findings have significant implications for metastasis and tumour progression in HNSCC.

Follicular adenoma presenting as lateral aberrant thyroid.

INTRODUCTION: True benign thyroid masses very rarely present as a solitary lateral neck mass. Different aetiological mechanisms have been proposed for such masses. CASE REPORT: We report a case of thyroid follicular adenoma that presented as a lateral neck mass. DISCUSSION: Ectopic thyroid tissue and metastases from primary thyroid carcinoma should always be considered in the differential diagnosis of lateral neck masses. Complete investigation should include complete blood tests to characterise the orthotopic thyroid gland.

A descriptive study of HIV-infected long-term surviving children in Barbados--a preliminary report.

OBJECTIVES: To describe the clinical and immunologic characteristics of human immunodeficiency virus type-1 (HIV-1)-infected children surviving to more than eight-years of age (long-survivors) before the introduction of antiretroviral therapy. METHODS: This report is based on all the long-term survivors from a prospective cohort of HIV-infected children born to HIV-positive women in Barbados during 1986-1995. Infants born to HIV-infected women were enrolled into this cohort at birth or at the time of diagnosis of HIV exposure in the postnatal period and followed-up at regular intervals. RESULTS: From a cohort of 44 HIV-infected children, 17 (38.6%) children survived to the age of eight years and beyond and were classified as long-term survivors. Median age of the sixteen long-term surviving children alive at the time of this report was 12 years (age range 8 - 16.7 years). At the age of 8 years, 17.6% of these children remained asymptomatic. Nine (52.9%) children had no immunodeficiency (CD4 counts >500 cells x 10(6)/L). Of the 16 long-term surviving children who were alive and had a median follow-up of 4.1 years (range 0.1 year to 8.5 years) after their eighth birthday, 37.5% had a CD4 cell count greater than 500 cells x 10(6)/L and had either no symptoms or only mild symptoms of HIV infection and were therefore categorized as the long-term non-progressors. CONCLUSIONS: In a small cohort of HIV-infected children, in the absence of antiretroviral therapy, only about one-third survived beyond eight years of age. On further follow-up of these long-term surviving children, over one-third had a slow rate of disease progression.

A descriptive study of HIV-infected long-term surviving children in Barbados--a preliminary report / Estudio Descriptivo de Niños Infectados por el VIH Sobrevivientes a Largo Plazo en Barbados Un Informe Preliminar

OBJECTIVES: To describe the clinical and immunologic characteristics of human immunodeficiency virus type-1 (HIV-1)-infected children surviving to more than eight-years of age (long-survivors) before the introduction of antiretroviral therapy. METHODS: This report is based on all the long-term survivors from a prospective cohort of HIV-infected children born to HIV-positive women in Barbados during 1986-1995. Infants born to HIV-infected women were enrolled into this cohort at birth or at the time of diagnosis of HIV exposure in the postnatal period and followed-up at regular intervals. RESULTS: From a cohort of 44 HIV-infected children, 17 (38.6%) children survived to the age of eight years and beyond and were classified as long-term survivors. Median age of the sixteen long-term surviving children alive at the time of this report was 12 years (age range 8 - 16.7 years). At the age of 8 years, 17.6% of these children remained asymptomatic. Nine (52.9%) children had no immunodeficiency (CD4 counts >500 cells x 10(6)/L). Of the 16 long-term surviving children who were alive and had a median follow-up of 4.1 years (range 0.1 year to 8.5 years) after their eighth birthday, 37.5% had a CD4 cell count greater than 500 cells x 10(6)/L and had either no symptoms or only mild symptoms of HIV infection and were therefore categorized as the long-term non-progressors. CONCLUSIONS: In a small cohort of HIV-infected children, in the absence of antiretroviral therapy, only about one-third survived beyond eight years of age. On further follow-up of these long-term surviving children, over one-third had a slow rate of disease progression

OBJETIVOS: Describir las características clínicas e inmunológicas de niños infectados por el VIH-1, que lograron sobrevivir hasta más de ocho años de edad (sobrevivientes a lago plazo) antes de la introducción de terapia antiretroviral. MÉTODOS: Este informe se basa en todos los sobrevivientes a largo plazo de una cohorte prospectiva de niños infectados por el VIH nacidos de mujeres VIH positivas en Barbados, durante los años 1986-1995. Los niños nacidos de mujeres infectadas por el VIH fueron enrolados en esta cohorte al nacer o en el momento de diagnóstico de exposición al VIH en el periodo postnatal, y seguidos a intervalos regulares. RESULTADOS: De una cohorte de 44 niños infectados por el VIH, 17 niños (38.6%) sobrevivieron hasta los ocho años de edad y más, clasificándoseles por ende como sobrevivientes a largo plazo. La edad media de los 16 niños sobrevivientes a largo plazo, aún vivos en el momento en que se hace este informe, fue de 12 años (rango de edad 8 ­ 16.7 años). A la edad de 8 años, el 17.6% de estos niños permanecían asintomáticos. Nueve de los niños (52.9%) no tenían inmunodeficiencia (conteos CD4 >500 células x 106/L). De los 16 niños sobrevivientes a largo plazo que estaban vivos y tuvieron un seguimiento de 4.1 años (en un rango de 0.1 año a 8.5 años) después de su octavo cumpleaños, 37.5% tuvo un conteo CD4 mayor de 500 células x 106/L, y bien no presentaban síntoma alguno de infección de VIH o se trataba sólo de síntomas leves, por lo cual fueron categorizados como no progresores de largo plazo. CONCLUSIONES: En una pequeña cohorte de niños infectados por el VIH, en ausencia de la terapia del antiretroviral, sólo aproximadamente un tercio logró sobrevivir más allá de ocho años de edad. Un seguimiento posterior de estos últimos niños sobrevivientes a largo plazo, mostró que más de un tercio presentaba un ritmo lento de progresión de la enfermedad

RNA profiling of cell-free saliva using microarray technology.

Saliva, like other bodily fluids, has been used to monitor human health and disease. This study tests the hypothesis that informative human mRNA exists in cell-free saliva. If present, salivary mRNA may provide potential biomarkers to identify populations and patients at high risk for oral and systemic diseases. Unstimulated saliva was collected from ten normal subjects. RNA was isolated from the cell-free saliva supernatant and linearly amplified. High-density oligonucleotide microarrays were used to profile salivary mRNA. The results demonstrated that there are thousands of human mRNAs in cell-free saliva. Quantitative PCR (Q-PCR) analysis confirmed the present of mRNA identified by our microarray study. A reference database was generated based on the mRNA profiles in normal saliva. Our finding proposes a novel clinical approach to salivary diagnostics, Salivary Transcriptome Diagnostics (STD), for potential applications in disease diagnostics as well as normal health surveillance.

Mortality among HIV-infected paediatric patients in Barbados.

Since the onset of the HIV epidemic, AIDS has become the leading cause of mortality in the paediatric age group in many developing countries. The main objective of this study was to review the mortality in HIV-infected paediatric patients in Barbados. It is a retrospective analysis of the hospitalization course of HIV-infected paediatric patients aged < 16 years who died during a 15-year period of surveillance. Using a specific database, information pertaining to number and duration of hospitalizations, and cause of death were analyzed. There were 39 (65%) deaths among 60 HIV-infected patients diagnosed during the period of study. Twenty-one (54%) were male and 18 (46%) were female. Twenty-seven (69%) case records were retrieved for analysis. The highest mortality (56%) was among patients aged < 1 year and between 1989 and 1995. Hospitalizations averaged three per patient. No patient received anti-retroviral therapy. Nineteen (70%) patients died during hospitalization on the paediatric ward. Lower respiratory tract infections suspected to be Pneumocystis carinii, gastroenteritis and septicaemia were the most frequent diagnoses at the time of death. The annual mortality ranged between 0 and 1.7 (mean 0.7) per 1000 live births. The overall mortality rate was high among HIV-infected paediatric patients, with lower respiratory tract infections being implicated as a major contributing cause of death. Results of this study definitely indicate a need for improved resources in the management of paediatric HIV/AIDS cases, especially focussing on the availability and administration of anti-retroviral therapy.

Leptospirosis occurring in two children after fresh water immersion

Leptospirosis is relatively uncommon in children. Two cases of severe leptospirosis occurred in teenaged boys who shared a common exposure via immersion in fresh water. While both patients had laboratory-confirmed leptospirosis, their symptoms differed in many respects.

An epidemic of congenital rubella in Barbados.

Rubella and congenital rubella syndrome (CRS) are preventable, but epidemics of rubella and CRS are not infrequent in the Caribbean and other developing countries. As a result of a surveillance system initiated after an epidemic of rubella in the Barbadian population in 1996, cases of CRS were identified and investigated. A total of seven cases of CRS were proven to be rubella IgM-positive. The infants were found to have a mean birthweight of 2587 g and a mean gestational age of 38 weeks. The clinical course, complications and outcome of those infants were documented and the cost of acute hospital care for each patient was also recorded. Cataracts in four infants, congenital heart disease in three and central nervous system abnormalities in five were the major clinical abnormalities. In four infants, two or more clinical systems were affected. The combined total hospital stay was 105 days (mean 15, range 0-44). A national effort to immunize all those at risk and a strict surveillance programme are essential to prevent future epidemics. This would lead to a significant reduction in the number of cases of rubella and CRS and could effect substantial savings in the national health budget.

An endemic of congenital rubella in Barbados

Rubella and congenital rubella syndrome (CRS) are preventable, but epidemics of rubella and CRS are not infrequent in the caribbean and other developing countries. As a result of a surveillance system initiated after an epidemic of rubella in the Barbadian population in 1996, cases of CRS were identified and investigated. A total of seven cases of CRS were proven to be rubella IgM-positive. The infants were found to have a mean borthweight of 2587 g and a mean gestational age of 38 weeks. The clinical course, complications and outcome of those infants were documented and the cost of acute hospital care for each patient was also recorded. Cataracts in four infants, congenital heart disease in three and central nervous system abnormalities in five were the major clinical abnormalities. In four infants, two or more clinical systems were affected. The combined total hospital stay was 105 days (mean 15, range 0-44). A national effort to immunize all those at risk and a strict surveillance programme are essential to prevent future epidemics. This would lead to a significant reduction in the number of cases of rubella and CRS and could effect substantial savings in the national health budget. (AU)

HIV infection among children in Barbados.

We studied a cohort of children with the human immunodeficiency virus (HIV) infection in Barbados in order to determine the prevalence of HIV infection, the clinical course including morbidity and mortality and the magnitude of the health care and social problems. Forty-seven children were diagnosed with HIV infection during the study period. The number of HIV infected children increased from 5 during 1981-85, to 14 during 1986-90, and to 21 during the 1991-95 period. The majority (91.5%) of infections resulted from perinatal transmission. Six (12.8%) cases remained asymptomatic and 41 (87.2%) were symptomatic with 19(46.3%) presenting in infancy, while 22 (53.5%) presented post-infancy. The median age at diagnosis (class P-2) was 13 months. Generalized lymphadenopathy (47.5%), hepatosplenomegaly (40.0%), failure to thrive (27.5%), persistent recurrent diarrhoea (15.0%), oral candidiasis (37.5%), Pneumocystis carinii pneumonia (37.5%), lymphoid interstitial pneumonia (12.5%) and progressive neurological disease (10.0%) were common HIV related conditions. Two children developed non-hodgkin's lymphoma. The median age at death for 23 children was 12 months, whereas the median survival after diagnosis was 4 months. Mortality was higher among those diagnosed in infancy (73.7%) as compared to those diagnosed post-infancy (42.8%). Pneumocystis carinii pneumonia was the most common (65.2%) cause of death. Paediatric HIV infection is rising and contributes considerably to infant mortality. In this study, children took longer to be symptomatic when compared to other reports. However, once symptomatic, they died early.

Leptospirosis occurring in two children after fresh water immersion.

Leptospirosis is relatively uncommon in children. Two cases of severe leptospirosis occurred in teenaged boys who shared a common exposure via immersion in fresh water. While both patients had laboratory-confirmed leptospirosis, their symptoms differed in many respects.

Human homologue of the Drosophila melanogaster lats tumour suppressor modulates CDC2 activity.

We have previously used mosaic flies to screen for tumour suppressors or negative regulators of cell proliferation. The cellular composition of these flies resembles that of cancer patients who are chimaeric individuals carrying a small number of mutated somatic cells. One of the genes we identified is the large tumour suppressor gene, lats (also known as wts), which encodes a putative serine/threonine kinase. Somatic cells mutant for lats undergo extensive proliferation and form large tumours in many tissues in mosaic adults. Homozygous mutants for various lats alleles display a range of developmental defects including embryonic lethality. Although many tumour suppressors have been identified in Drosophila melanogaster, it is not clear whether these fly genes are directly relevant to tumorigenesis in mammals. Here, we have isolated mammalian homologues of Drosophila lats. Human LATS1 suppresses tumour growth and rescues all developmental defects, including embryonic lethality in flies. In mammalian cells, LATS1 is phosphorylated in a cell-cycle-dependent manner and complexes with CDC2 in early mitosis. LATS1-associated CDC2 has no mitotic cyclin partner and no kinase activity for histone H1. Furthermore, lats mutant cells in Drosophila abnormally accumulate cyclin A. These biochemical observations indicate that LATS is a novel negative regulator of CDC2/cyclin A, a finding supported by genetic data in Drosophila demonstrating that lats specifically interacts with cdc2 and cyclin A.

Mice deficient of Lats1 develop soft-tissue sarcomas, ovarian tumours and pituitary dysfunction.

The lats gene has been identified as a tumour suppressor in Drosophila melanogaster using mosaic screens. Mosaic flies carrying somatic cells that are mutant for lats develop large tumours in many organs. The human LATS1 homologue rescues embryonic lethality and inhibits tumour growth in lats mutant flies, demonstrating the functional conservation of this gene. Biochemical and genetic analyses have revealed that LATS1 functions as a negative regulator of CDC2 (ref. 3). These data suggest that mammalian LATS1 may have a role in tumorigenesis. To elucidate the function of mammalian LATS1, we have generated Lats1-/- mice. Lats1-/- animals exhibit a lack of mammary gland development, infertility and growth retardation. Accompanying these defects are hyperplastic changes in the pituitary and decreased serum hormone levels. The reproductive hormone defects of Lats1-/- mice are reminiscent of isolated LH-hypogonadotropic hypogonadism and corpus luteum insufficiency in humans. Furthermore, Lats1-/- mice develop soft-tissue sarcomas and ovarian stromal cell tumours and are highly sensitive to carcinogenic treatments. Our data demonstrate a role for Lats1 in mammalian tumorigenesis and specific endocrine dysfunction.

Haemoglobin electrophoresis patterns in Barbados.

Despite the extensive data on haemoglobinopathies and their widespread geographic distribution, the number of prospective Caribbean studies which document the prevalence of haemoglobinopathies from birth are few. The purpose of this cohort study was to document the prevalence of haemoglobinopathies in newborn infants in Barbados. One thousand successively collected cord bloods of newborn infants were screened for haemoglobinopathies using the Paragon acid electrophoresis technique. Seventeen infants were retested at 1 year of age to confirm the diagnosis. Three mothers could not be located so their infants' diagnoses could not be confirmed. From the 997 blood samples with conclusive results, a haemoglobinopathy was found in 72 (7%) samples. Laboratory analysis revealed: 925 patients (93%) with Hb AA, 41 (4%) with Hb AS, 27 (2.7%) with Hb AC, 2 (0.2%) with Hb SS, 1 (0.1%) with Hb CC and 1 (0.1%) with Hb SC. The prevalence of the sickle gene and number of cases of Sickle Cell anaemia in the Barbadian population is less than has been reported from other regional territories.

Congenital solitary non-parasitic cyst of the liver.

Although non-parasitic cysts of the liver have often been described in adults, solitary non-parasitic cysts are rare in infants. We report a 17-month-old child with a large hepatic cyst.