A case of benign periosteal chondroma seeding into humeral medullary bone via percutaneous needle biopsy tract.

We report an occurrence of periosteal chondroma seeding into the medulla of humerus via percutaneous needle biopsy tract. To our knowledge, this is the first described case of benign cartilage tumour biopsy tract seeding in the literature. We discuss the clinical, radiological and histological features of periosteal chondroma, as well as the diagnostic challenges associated with distinguishing this entity from periosteal chondrosarcoma. Finally, we briefly discuss the safety of imaging-guided percutaneous needle biopsy and methods to minimize the risk of iatrogenic tumour seeding.

An examination of signs of disease progression in survivors of the Sydney Blood Bank Cohort (SBBC).

BACKGROUND: The Sydney Blood Bank Cohort (SBBC) was infected between 1981 and 1984 with a nef/LTR defective strain of HIV-1. Different responses to HIV-1 infection have emerged between cohort members in the last 5 years. Three recipients (C135, C64 and C49) remain asymptomatic, have normal CD4 T cell counts, below detection (BD) viral loads (VL), remain therapy naive and are termed long-term non-progressors (LTNP). The donor (D36) and the two recipients (C98 and C54) have significantly declining CD4 T cell counts, detectable VL and are now long-term survivors (LTS). In contrast, in the SA cohort, comparison study group for the SBBC, five of 24 remain therapy naïve after 15 years infection with HIV-1 and all have detectable VL. OBJECTIVES: This paper examines different outcomes to long-term infection with HIV-1 in the SBBC and provides a brief overview of the therapy naïve in a comparison study group, the SA cohort. STUDY DESIGN: Retrospective epidemiological follow-up of the SBBC and the SA cohort has been conducted for >15 years. Analysis of CD4 T cell counts, VL and intermittent monitoring of HIV-specific proliferative responses are reviewed. Viral sequence changes in the SBBC will be considered. RESULTS: Prior to therapy D36 had a CD4 T cell count of 160/mm(3) and plasma VL of 9900 copies/ml while C98 had a CD4 T cell count of 387/mm(3) and plasma VL of 11491 copies/ml. After 1 month of therapy, plasma VL was BD (<400 copies/ml) and both showed significant increase in CD4 T cell counts. Molecular changes have occurred in D36 and C98 viral strains, the most recently evolved quasispecies have larger deletions in the nef/LTR region. CONCLUSIONS: Infection with nef/LTR deleted HIV-1 has resulted in slower disease progression for the SBBC. The three LTNP have maintained normal low levels of activated CD8 T cells and strong HIV-specific proliferative responses to HIV-1 p24, which are associated with control of viral replication.

HLA and other host factors in transfusion-acquired HIV-1 infection.

The host and viral factors that underlie infection with HIV-1 vary considerably with some individuals progressing to AIDS within 3 to 5 years after infection, whereas others remain clinically asymptomatic for over 10 years. Host factors that may contribute to disease progression include HLA and allelic variants of the chemokine receptors CCR5 and CCR2, which have been shown to influence both long-term survival and rapid progression. In this study, we have examined the contribution of HLA and polymorphisms in CCR5 and CCR2 to long-term survival in transfusion-acquired HIV-1-infected individuals. We have found a higher number of HLA-A32 and -A25 alleles but a lower number of the HLA-B8 allele in the study group compared with the frequencies seen in the HIV-1-negative Australian caucasian population. However, there was no apparent contribution by allelic variants of CCR5 and CCR2 to long-term survival and the combined influence of HLA and CCR polymorphisms could not be evaluated in this relatively small (n = 20) group of study subjects. The results of this work support a role for HLA in long-term nonprogression though the presence in the Sydney Blood bank Cohort of nef-defective HIV-1 may confound associations between certain HLA alleles and long-term survival in the face of infection with HIV-1.

Effect of long-term infection with nef-defective attenuated HIV type 1 on CD4+ and CD8+ T lymphocytes: increased CD45RO+CD4+ T lymphocytes and limited activation of CD8+ T lymphocytes.

Members of the Sydney Blood Bank Cohort (SBBC) have been infected with an attenuated strain of HIV-1 with a natural nef/LTR mutation and have maintained relatively stable CD4+ T lymphocyte counts for 14-18 years. Flow cytometric analysis was used to examine the phenotype of CD4+ and CD8+ T lymphocytes in these subjects, including the immunologically important naive (CD45RA+CD62L+), primed (CD45RO+), and activated (CD38+HLA-DR+ and CD28-) subsets. The median values were compared between the SBBC and control groups, comprising age-, sex-, and transfusion-matched HIV-1-uninfected subjects; transfusion-acquired HIV-1-positive LTNPs; and sexually acquired HIV-1-positive LTNPs. Members of the SBBC not only had normal levels of naive CD4+ and CD8+ T lymphocytes, but had primed CD45RO+ CD4+ T lymphocytes at or above normal levels. Furthermore, these primed cells expressed markers suggesting recent exposure to specific antigen. SBBC members exhibited variable activation of CD8+ T lymphocytes. In particular, SBBC members with undetectable plasma HIV-1 RNA had normal levels of activated CD8+ T lymphocytes. Therefore, the result of long-term infection with natural nef/LTR mutant HIV-1 in these subjects suggests a decreased cytopathic effect of attenuated HIV-1 on susceptible activated CD4+ T lymphocyte subsets in vivo, and minimal activation of CD8+ T lymphocytes.

Identification of a new recipient in the Sydney Blood Bank Cohort: a long-term HIV type 1-infected seroindeterminate individual.

We have reported previously a cohort of long-term survivors of HIV-1 infection, known as the Sydney Blood Bank Cohort, who received HIV-1-positive blood from a common infected donor. A new recipient, C135, has been identified. This recipient became infected after receiving blood donated during the presumed time of seroconversion of the donor in February 1981. C135 has been infected for more than 18 years without signs of disease progression. The virus load in this recipient has remained below the detectable level (<20 RNA copies/ml of plasma) and repeated Western blot analyses have given an indeterminate result. By booster PCR techniques we have demonstrated that this individual is infected with HIV-1 and have characterized the viral nef and nef/LTR region sequences present. The strain of HIV-1 identified contains deletions of 88 bp from the nef alone region and a total of 139 bp deleted from the nef/LTR overlap and LTR regions. The LTR contains three wild-type Sp1 transcription factor-binding sites, the 3' wildtype NF-kappaB site, and a duplicated Sp1 and NF-kappaB region. A truncated Nef protein of only 19 amino acids is encoded. The deletions and rearrangements in the nef gene and LTR sequences are characteristic of Sydney Blood Bank Cohort strains of virus. The identification of C135 increases the Sydney Blood Bank Cohort size to nine individuals and represents a rare example of a genuine, long-term HIV-1 infection accompanied by indeterminate anti-HIV-1 serology.

The Sydney Blood Bank Cohort: a case-control study using a transfused HIV-1 seronegative group.

PURPOSE: To compare the immunological function of the Sydney Blood Bank Cohort (SBBC), a unique group of individuals who were all infected with a similar, attenuated strain of HIV-1, with a matched HIV-1 seronegative control group. To establish whether the asymptomatic state of the SBBC, in 1996, was likely to continue, and whether the SBBC were free from immunological signs of disease progression. METHODS: A prospective case-control design using a matched transfused HIV-1 seronegative control group. Immunological testing was performed and compared across the groups. These measurements included CD4+, CD8+, CD3 + subsets, total lymphocytes, beta-2-microgloublin (beta2M), and neopterin. RESULTS: Significant differences were observed between the SBBC and the controls, particularly CD4% (p < 0.05), CD8 counts (p < 0.01), and CD4:CD8 ratios (p < 0.001). CONCLUSIONS: The results suggested that, as a group, the SBBC remained asymptomatic 12 to 16 years after infection with HIV-1. However, elevated CD8+ T lymphocytes, together with decreasing CD4%, suggested that some SBBC members were showing early immunologicalsigns of disease progression during late 1996, confirmed by recent (1998) follow-up studies.

Immunologic and virologic status after 14 to 18 years of infection with an attenuated strain of HIV-1. A report from the Sydney Blood Bank Cohort.

BACKGROUND AND METHODS: The Sydney Blood Bank Cohort consists of a blood donor and eight transfusion recipients who were infected before 1985 with a strain of human immunodeficiency virus type 1 (HIV-1) with a deletion in the region in which the nef gene and the long terminal repeat overlap. Two recipients have died since 1994, at 77 and 83 years of age, of causes unrelated to HIV infection; one other recipient, who had systemic lupus erythematosus, died in 1987 at 22 years of age of causes possibly related to HIV. We present longitudinal immunologic and virologic data on the six surviving members and one deceased member of this cohort through September 30, 1998. RESULTS: The five surviving recipients remain asymptomatic 14 to 18 years after HIV-1 infection without any antiretroviral therapy; however, the donor commenced therapy in February 1999. In three recipients plasma concentrations of HIV-1 RNA are undetectable (<200 copies per milliliter), and in two of these three the CD4 lymphocyte counts have declined by 9 and 30 cells per cubic millimeter per year (P=0.3 and P=0.5, respectively). The donor and two other recipients have median plasma concentrations of HIV-1 RNA of 645 to 2850 copies per milliliter; the concentration has increased in the donor (P<0.001). The CD4 lymphocyte counts in these three cohort members have declined by 16 to 73 cells per cubic millimeter per year (P<0.001). In the recipient who died after 12 years of infection, the median plasma concentration of HIV-1 RNA was 1400 copies per milliliter, with a decline in CD4 lymphocyte counts of 17 cells per cubic millimeter per year (P=0.2). CONCLUSIONS: After prolonged infection with this attenuated strain of HIV-1, there is evidence of immunologic damage in three of the four subjects with detectable plasma HIV-1 RNA. The CD4 lymphocyte counts appear to be stable in the three subjects in whom plasma HIV-1 RNA remains undetectable.

Lymphoproliferative immune function in the Sydney Blood Bank Cohort, infected with natural nef/long terminal repeat mutants, and in other long-term survivors of transfusion-acquired HIV-1 infection.

OBJECTIVES: To assess T-helper cell immune function (proliferation) in members of the Sydney Blood Bank Cohort (SBBC) compared with other individuals with transfusion- and sexually acquired HIV-1 infection and with matched HIV-negative controls. DESIGN AND METHODS: Decreasing CD4 counts and T-helper cell function are associated with disease progression. Peripheral blood mononuclear cells (PBMC) from study subjects were assayed for in vitro proliferative responses to HIV-1-derived antigens, recall antigens and alloantigen. T-helper cell function and CD4 counts in members of the SBBC were followed longitudinally. RESULTS: Proliferative responses and CD4 counts from members of the SBBC were similar to or better than those of other transfusion- or sexually-acquired HIV-1-positive long-term non-progressors (LTNP), including the HIV-negative matched SBBC control groups. However, individuals with disease progression had reduced or undetectable proliferative responses to recall antigens but a conserved response to alloantigen; they also had low CD4 counts and low CD4:CD8 ratios. In the SBBC, these immune parameters were usually stable over time. CONCLUSIONS: The unique SBBC with natural nef/long terminal repeat deletions in the HIV-1 genome were genuine LTNP without showing signs of disease progression. They appeared to be a group distinct from the tail-end of the normal distribution of disease progression rates, and may remain asymptomatic indefinitely. The SBBC virus may form the basis of a live attenuated immunotherapeutic or immunoprophylactic HIV vaccine.

Human placental syncytiotrophoblast microvillous membranes impair maternal vascular endothelial function.

OBJECTIVE: To investigate the hypothesis that, should there be an increase in deported syncytiotrophoblast microvillous membrane fragments in pre-eclampsia, it may cause maternal vascular endothelial dysfunction. DESIGN: Syncytiotrophoblast microvillous membrane (STBM) vesicles, prepared from normal term placentae, were perfused through small subcutaneous arteries isolated from fat biopsies obtained at caesarean section. Endothelial function of these arteries was studied by determining acetylcholine-induced relaxation after preconstriction with noradrenaline. As controls, physiological buffer or red blood cell membranes in physiological buffer were used and endothelial function similarly estimated. Transmission electron microscopy was performed on arteries after perfusion. SAMPLE: STBM vesicles, isolated from the placentae of three healthy women undergoing elective caesarean section for reasons unrelated to pre-eclampsia, were suspended in physiological buffer. Subcutaneous fat arteries were obtained from a separate group of 13 normotensive pregnant women, also undergoing elective caesarean section at term. RESULTS: Perfusion with red blood cell membranes or physiological buffer had no significant effect on the concentration dependent relaxation in arteries preconstricted with noradrenaline. However, after 2 h perfusion with STBM vesicles, arteries showed a significant reduction in relaxation to acetylcholine, indicative of altered endothelial function. Transmission electron microscopy of arteries perfused with STBM vesicles confirmed endothelial disruption. CONCLUSIONS: STBM vesicle perfusion specifically altered the relaxation response of preconstricted maternal subcutaneous fat arteries to acetylcholine, suggesting an alteration in endothelial dependent relaxation. Deported microvilli may therefore be capable of producing endothelial cell damage and endothelial dysfunction observed in the maternal syndrome of pre-eclampsia.

Myogenic and flow-mediated responses in isolated mesenteric small arteries from pregnant and nonpregnant rats.

OBJECTIVES: Responses to pressure, agonist-induced constriction, endothelium-dependent vasodilators, and shear stress were investigated in resistance-sized mesenteric arteries in vitro from late-pregnant and nonpregnant rats. STUDY DESIGN: Myogenic tone was determined in arteries mounted on a pressure myograph by evaluating the response to incremental increases in luminal pressure in resting arteries and arteries preconstricted with norepinephrine (10(-6) mol/L). Flow-mediated dilation was also investigated in the presence and absence of a nitric oxide synthase inhibitor, L-N(omega)-nitro-L-arginine methyl ester. Constrictor responses to norepinephrine (10(-9) to 10(-5) mol/L), were examined with a small vessel myograph. Responses of preconstricted arteries to acetylcholine (10(-9) to 10(-5) mol/L), bradykinin (10(-9) to 10(-5) mol/L), and sodium nitroprusside (10(-9) to 10(-5) mol/L) were also assessed. RESULTS: Myogenic tone was only demonstrable in response to increasing pressure when arteries were preconstricted with norepinephrine (10(-6) mol/L) and was similar in arteries from both pregnant and nonpregnant rats. Flow-mediated dilation was greater in pregnant rats and was reduced by L-N(omega)-nitro-L-arginine methyl ester. Arteries from the pregnant rats demonstrated a reduced constrictor response to norepinephrine. Responses to acetylcholine were similar in both groups, but arteries from the pregnant rats showed enhanced relaxation to bradykinin. CONCLUSIONS: The data substantiate previous studies indicating reduced constrictor responses in pregnancy but provide no evidence to suggest that blunted myogenic responses contribute to reduced vascular resistance in pregnancy. The results indicate that flow-mediated nitric oxide release may contribute to vasodilation in pregnant rats. Different responses to two endothelium-dependent vasodilators suggest that specific alterations in signal transduction pathways may influence nitric oxide synthesis in pregnancy.

Nitric oxide is involved in flow-induced dilation of isolated human small fetoplacental arteries.

OBJECTIVES: The aim of this study was to determine the dilation that occurs in response to increments of intraluminal flow in isolated human small fetoplacental arteries and to investigate the role played by nitric oxide. STUDY DESIGN: Small fetoplacental arteries (mean luminal diameter 482 +/- 31 micrometers, n = 17, at zero flow and pressure) were dissected from samples of placental tissue obtained from normal term vaginal deliveries and elective term cesarean sections for breech presentation. The arteries were mounted on a pressure myograph, and the response to increasing intraluminal flow was investigated in the presence and absence of a nitric oxide synthase inhibitor (N-omega-nitro-L-arginine methyl ester, 10(-4) mol/L). Basal tone was assessed in a separate group of arteries (n=7) by the removal of extracellular calcium. RESULTS: The presence of significant basal tone was demonstrated in these arteries. The arteries dilated in response to increasing luminal flow, and the dilation was significantly reduced by inhibition of nitric oxide synthase (control, 5.5% +/- 1.0% increase in artery diameter, n=10, vs 0.95 +/- 0.94, n=10, in the presence of N-omega-nitro-L-arginine methyl ester, 10(-4) mol/L, p<0.01). CONCLUSIONS: The data substantiate previous indirect studies suggesting that nitric oxide plays a role in the fetoplacental circulation. Flow-induced nitric oxide release in the stem villous arteries may make an important contribution to maintenance of this low-resistance circulation.

Genomic structure of an attenuated quasi species of HIV-1 from a blood transfusion donor and recipients.

A blood donor infected with human immunodeficiency virus-type 1 (HIV-1) and a cohort of six blood or blood product recipients infected from this donor remain free of HIV-1-related disease with stable and normal CD4 lymphocyte counts 10 to 14 years after infection. HIV-1 sequences from either virus isolates or patient peripheral blood mononuclear cells had similar deletions in the nef gene and in the region of overlap of nef and the U3 region of the long terminal repeat (LTR). Full-length sequencing of one isolate genome and amplification of selected HIV-1 genome regions from other cohort members revealed no other abnormalities of obvious functional significance. These data show that survival after HIV infection can be determined by the HIV genome and support the importance of nef or the U3 region of the LTR in determining the pathogenicity of HIV-1.

Nitric oxide synthase activities in placental tissue from normotensive, pre-eclamptic and growth retarded pregnancies.

OBJECTIVE: To measure nitric oxide synthase activity in tissues from the placenta, placental bed and umbilical cord at delivery in normal and complicated pregnancies. DESIGN: A prospective blinded study. SETTING: The obstetric departments of three London teaching hospitals. SUBJECTS: Samples of whole placenta, dissected stem villous arteries, umbilical cord vessels and the placental bed of the uterus were collected at delivery and assayed for nitric oxide synthase activity. Samples of placenta were taken from ten normotensive, six pre-eclamptic and eight growth retarded pregnancies, and stem villous arteries from a further seven normotensive pregnancies. RESULTS: There was minimal placental bed nitric oxide synthase activity in each group. Placental villous homogenates from pregnancies complicated by pre-eclampsia and fetal growth retardation had significantly lower activities of nitric oxide synthase than those from normotensive women with appropriately grown babies. There were no significant differences in calcium dependent or calcium independent nitric oxide synthase activities in the umbilical vein and artery in the normal or in the pre-eclamptic groups. However, there was significantly more calcium dependent than calcium independent nitric oxide synthase in the umbilical veins in all groups. CONCLUSIONS: Local nitric oxide production in the placental bed of the uterus is unlikely to contribute substantially to the low resting vascular tone in the uteroplacental circulation. However, a relative deficiency of placental nitric oxide in pregnancies complicated by fetal growth retardation and pre-eclampsia may contribute to the development of the high impedance fetoplacental circulation found in these conditions.

Heterosexually acquired HIV infection in female blood donors: case series between 1985-1990.

The case histories aimed to describe the risk behaviours of a series of seven Australian women who acquired the human immunodeficiency virus (HIV) through heterosexual contact. Between 1985 and 1990 eight HIV antibody positive female donors were identified through routine HIV antibody screening at the NSW Red Cross Blood Transfusion Service. These donors were recalled and interviewed to assess risk factors for HIV and establish how and/or why the declaration form and the interview process prior to donation did not identify a risk factor. The most likely risk factor in seven cases was then assessed by the Blood Bank to be heterosexual transmission. Histories for three cases were based on the standard risk assessment interview at the Blood Bank and four case histories were based on additional interviews conducted independently from the Blood Bank with informed consent.