Long-term clinical, virological and immunological outcomes following planned treatment interruption in HIV-infected children.

OBJECTIVES: Planned treatment interruption (PTI) of antiretroviral therapy (ART) in adults is associated with adverse outcomes. The PENTA 11 trial randomized HIV-infected children to continuous ART (CT) vs. CD4-driven PTIs. We report 5 years' follow-up after the end of main trial. METHODS: Post-trial, all children resumed ART. Clinical, immunological, virological and treatment data were collected annually. A sub-study investigated more detailed immunophenotype. CT and PTI arms were compared using intention-to-treat. Laboratory parameters were compared using linear regression, adjusting for baseline values; mixed models were used to include all data over time. RESULTS: In all, 101 children (51 CT, 50 PTI) contributed a median of 7.6 years, including 5.1 years of post-trial follow-up. Post-trial, there were no deaths, one pulmonary tuberculosis and no other CDC stage B/C events. At 5 years post-trial, 90% of children in the CT vs. 82% in the PTI arm had HIV RNA < 50 copies/mL (P = 0.26). A persistent increase in CD8 cells was observed in the PTI arm. The sub-study (54 children) suggested that both naïve and memory populations contributed to higher CD8 cells following PTI. Mean CD4/CD8 ratios at 5 years post-trial were 1.22 and 1.08 in CT and PTI arms, respectively [difference (CT - PTI) = -0.15; 95% CI: -0.34-0.05), P = 0.14]. The sub-study also suggested that during the trial and at early timepoints after the end of the trial, reduction in CD4 in the PTI arm was mainly from loss of CD4 memory cells. CONCLUSIONS: Children tolerated PTI with few long-term clinical, virological or immunological consequences.

Asymptomatic elevated parathyroid hormone level due to immunoassay interference.

BACKGROUND: Parathyroid hormone (PTH) measurement using immunoassays is inherently vulnerable to interferences due to the presence of different proteins such as heterophile antibodies, human anti-animal antibodies, auto-analyte antibodies, the rheumatoid factor, and others. The frequency of immunoassay interference can be as high as 6%. We report the case of a patient showing persistent high levels of PTH without impact on calcium and bone metabolism. CASE PRESENTATION: The patient was a 59-year-old asymptomatic woman who consistently showed elevated PTH levels (385-482 pg/ml) using the Roche Elecsys (Cobas e-411) and ADVIA Centaur assays, with normal calcium, phosphorus, vitamin D, and renal function parameters. She had no history of fractures, nephrolithiasis, gastrointestinal complaints, renal insufficiency, or autoimmune diseases. Her physical examination revealed no abnormalities. Biomarkers of bone metabolism were within the reference range. To rule out falsely elevated PTH levels, we initially performed serial dilutions using both assays, which revealed nonlinearity. After a polyethylene glycol precipitation test, less than 10% of PTH was recovered from the supernatant. These results suggested the presence of heterophile antibodies as the cause of the falsely elevated PTH levels. CONCLUSION: Physicians should be aware of this issue in order to avoid unnecessary clinical investigations and inappropriate treatments.

Severe bone microarchitecture deterioration in a family with hereditary neuropathy: evidence of the key role of the mechanostat.

In this report, we present three cases of individuals from the same family with a diagnosis of CMT with severe tibia bone microarchitecture deterioration assessed by HR-pQCT. Charcot-Marie-Tooth disease (CMT) or hereditary neuropathy involves both motor and sensory nerves. Falls are often the first manifestation in these patients and represent an important risk factor for fracture. The reduction of mechanical input on bone inhibits bone formation by osteoblasts and accelerates bone resorption by osteoclasts, leading to disuse osteoporosis. We report three cases of individuals from the same family with a diagnosis of CMT with severe tibia bone microarchitecture deterioration assessed by high-resolution peripheral quantitative computed tomography (HR-pQCT). This affectation was exclusive to the tibia; the radius remained undamaged, showing the consequences of the lack of mobility and mechanical stimulation. Physical activity and rehabilitation, in addition to adequate calcium and vitamin D supplementation, may play an essential role in the management of this disease.

Significant bone loss after stopping long-term denosumab treatment: a post FREEDOM study.

We evaluate 38 elderly women who had received long-term denosumab treatment after stopping the drug. Taking into account the gain during treatment and the loss after stopping treatment, they lost 35.5% of the total gain in the spine, 44.6% of the total gain in the femoral neck, and 103.3% in the total hip. INTRODUCTION: Denosumab (DMAb) is a soluble inhibitor of the receptor activator of nuclear factor-kappaB ligand (RANKL) and, therefore, does not incorporate into the bone matrix. Consistently, DMAb discontinuation is associated with reversal of the effects attained with treatment. PURPOSE: The aim of this study is to assess changes in BMD after a year of discontinuation of DMAb in a group of postmenopausal women treated with DMAb for 7 or 10 years. Secondly, is to evaluate the occurrence of fragility fractures. METHODS: Women who had participated in the FREEDOM study and its extension were invited to participate in this follow-up study. BMD at LS and hip and spine X-rays were obtained. Results were compared to the last value obtained while in treatment to assess changes after discontinuation. RESULTS: Thirty-eight women, mean age: 81 ± 3.4 years completed study procedures; none had received bisphosphonates after stopping DMAb. Mean gap time between DMAb last dose and the follow-up visit was 17 months (range 16-20 months). Bone mineral density (BMD) decreased significantly in all regions: - 8.1% in LS, - 6% in FN, and - 8.4% in TH. Five (5/38, 13.15%) patients had a fragility fracture, one suffered a wrist fracture, and four experienced vertebral fractures. Three patients suffered one vertebral fracture and one of them had two vertebral fractures. Laboratory results showed the following mean values: CTX = 996 ± 307 pg/ml (normal values 550 ± 226 pg/ml); osteocalcin = 55.2 ± 18.6 ng/ml (normal value 42 ng/ml); and 25 OH vitamin D = 23.7 ± 6.9 ng/ml. CONCLUSION: Our results describe the rapid bone loss occurring after cessation of denosumab treatment. Further studies are needed to assess if patients have a higher risk of fracture after stopping DMAb and if so, which patients have the highest risk, and assess the role of transitioning to bisphosphonates in the long term.

Retreatment with teriparatide: our experience in three patients with severe secondary osteoporosis.

Teriparatide is a drug for the treatment of osteoporosis which is licensed for use for up to 24 months. There is little experience with retreatment. The aim of this study was to evaluate, in three patients with severe secondary osteoporosis, the response to a second cycle of teriparatide regarding bone mineral density (BMD) and osteocalcin. Case 1 : A 62-year-old woman with multiple vertebral fractures has received corticoids for a long time. After starting teriparatide, her BMD and osteocalcin increased. She then received ibandronate for 3 years but her BMD declined. After a second treatment with teriparatide, her BMD increased again (18%). Case 2 : A 60-year-old woman with severe osteoporosis in lumbar spine (LS) (T-score - 4.5) had received corticoids for a long time and had celiac disease. After starting teriparatide, her BMD improved by 11.7%. She then received zoledronic acid for 15 months, but bone density decreased, so she was retreated with teriparatide. BMD had a slightly higher increase than after the first cycle (12.6%). Case 3 : A 60-year-old woman consulted for osteoporosis (LS T-score - 5.3), several fractures, and hyperthyroidism. She started teriparatide with improvement in BMD (39%). After 24 months, she received ibandronate for 1 year, but as her BMD declined, she was retreated with teriparatide. BMD showed an increase of 15%. The indication of a second cycle of treatment with teriparatide in three patients was effective in increasing BMD. Additional studies are needed to further identify the benefits and safety of retreatment with teriparatide.

Bone microarchitecture in Rett syndrome and treatment with teriparatide: a case report.

We present the case of a 28-year-old female Rett syndrome patient with low bone mass and a recent fracture who was successfully treated with teriparatide. Bone mineral density and microarchitecture substantially improved after treatment. Rett syndrome (RTT), an X-linked progressive neuro-developmental disorder caused by mutations in the methyl-CpG-binding 2 (MECP2) gene, has been consistently associated with low bone mass. Consequently, patients with RTT are at increased risk of skeletal fractures. Teriparatide is a bone-forming agent for the treatment of osteoporosis that has demonstrated its effectiveness in increasing bone strength and reducing the risk of fractures in postmenopausal women, but, recently, its positive action has also been reported in premenopausal women. We present the case of a 28-year-old female RTT patient with low bone mass and a recent fracture who was successfully treated with teriparatide. Both bone mass measured by DXA and microarchitecture assessed by high resolution peripheral computed tomography (HR pQCT) were substantially improved after treatment.

Prospective roles for Canadian oncology nurses in breast cancer rapid diagnostic clinics.

The introduction of rapid diagnostic clinics for breast cancer increases oncology nurses' (ONs) responsibility for patient education and coordination of multidisciplinary care. Developed as an outcome of the E-Mentorship Oncology Nursing Program, this paper proposes new roles for these nurses to respond effectively and competently to such diagnostic innovation. The Oslo Manual Conceptual Framework of Innovation inspired the idea of change in prospective ONs' roles, corroborated by the Canadian Association of Nurses in Oncology's Standards of Practice and Competencies. New roles for ONs that are informed by the domain of information dynamics and evidence-based care are proposed.

Evaluation of bone microarchitecture by high-resolution peripheral quantitative computed tomography (HR-pQCT) in hemodialysis patients.

UNLABELLED: Hemodialyzed patients have decreased bone strength not completely characterized. We evaluated bone microarchitecture in hemodialysis patients and compared it to that of subjects without renal disease by high-resolution peripheral quantitative computed tomography (HR-pQCT). Hemodialysis patients have a marked decreased in cortical density, thickness, and area with significant reduction in trabecular parameters that correlated with the severity of secondary hyperparathyroidism only in women. INTRODUCTION: Although fracture risk is greatly increased in dialysis patients, the corresponding decreased in bone strength has not been completely characterized. METHODS: We evaluated volumetric bone mineral density (vBMD) and bone microstructure by HR-pQCT at the distal radius and tibia in 50 hemodialyzed (HD) patients (30 females, mean age 53.2 ± 6 years and 20 males, mean age 59.1 ± 11 years) and 50 sex- and age-matched controls. RESULTS: At the distal radius HD, women showed a 29% reduction in total and trabecular density and trabecular bone volume fraction (p < 0.0001) compared to controls. Trabecular number was reduced by 25% (p < 0.0001), while trabecular separation was increased by 51%. Cortical thickness (-40%, p < 0.0001) and cortical area (-42%, p < 0.0001) were the parameters most reduced, while compact density was the parameter least reduced (-15%, p < 0.0001). Similar findings were found at the tibia. In HD men, HR-pQCT at the distal radius and tibia showed a reduction in volumetric density and microstructure parameters to a lesser extent than in women. In the hemodialyzed group, cortical thickness at the radius was negatively correlated with age both in women and men. At the distal radius and tibia, we found significant negative correlations between Log iPTH and total alkaline phosphatase with cortical vBMD(r = -0.48, p < 0.01; r = -0.69, p < 0.001), thickness (-0.37, p < 0.05; r = -0.60, p < 0.001), and area ((r = -0.43, p = 0.02; r = -0.65, p < 0.001) but only in women. CONCLUSION: We conclude that hemodialysis patients have a marked decreased in cortical density, thickness, and area with significant reduction in trabecular parameters that correlated with the severity of secondary hyperparathyroidism only in women.

Scientific and popular health knowledge in the education work of community health agents in Rio de Janeiro shantytowns.

Health education for socially marginalized populations challenges the efficacy of existing strategies and methods, and the pertinence of the educational and philosophical principles that underpin them. The Brazilian Community Health Agents Initiative (CHAI) hires residents of deprived marginalized communities to undertake health promotion and education in their communities. The ultimate goal of the CHAI is to connect populations with the public healthcare system by promoting social re-affiliation, protecting civil rights and enhancing equity of access to health services. In this article, we present the education work of community health agents through interplay between popular and scientific health knowledge in nine Rio de Janeiro shantytowns. A critical ethnographic research design, using thematic analysis, allowed us to explore agents' education work to enhance family health literacy in shantytowns. Local culture and social practices inspire Agents to create original strategies to reconcile forms of health knowledge in their work.

Regulatory T cells and chronic immune activation in human immunodeficiency virus 1 (HIV-1)-infected children.

The function of CD4(+) T cells with regulatory activity (T(regs)) is the down-regulation of immune responses. This suppressive activity may limit the magnitude of effector responses, resulting in failure to control human immunodeficiency virus 1 (HIV-1) infection, but may also suppress chronic immune activation, a characteristic feature of HIV-1 disease. We evaluated the correlation between viral load, immune activation and T(regs) in HIV-1-infected children. Eighty-nine HIV-1-infected children (aged 6-14 years) were included in the study and analysed for HIV-1 plasmaviraemia, HIV-1 DNA load, CD4 and CD8 cell subsets. T(reg) cells [CD4(+)CD25(high)CD127(low) forkhead box P3 (FoxP3(high))] and CD8-activated T cells (CD8(+)CD38(+)) were determined by flow cytometry. Results showed that the number of activated CD8(+)CD38(+)T cells increased in relation to HIV-1 RNA plasmaviraemia (r = 0·403, P < 0·0001). The proportion of T(regs) also correlated positively with HIV-1 plasmaviraemia (r = 0·323, P = 0·002), but correlated inversely with CD4(+) cells (r = -0·312, P = 0·004), thus suggesting a selective expansion along with increased viraemia and CD4(+) depletion. Interestingly, a positive correlation was found between the levels of T(regs) and CD8(+)CD38(+)T cells (r = 0·305, P = 0·005), and the percentage of T(regs) tended to correlate with HIV-1 DNA load (r = 0·224, P = 0·062). Overall, these findings suggest that immune activation contributes to the expansion of T(reg) cells. In turn, the suppressive activity of T(regs) may impair effector responses against HIV-1, but appears to be ineffective in limiting immune activation.

Diagnostic, treatment, and follow-up of osteoporosis-position statement of the Latin American Federation of Endocrinology.

The Latin American Federation of Endocrinology position statement on osteoporosis was developed by endocrinologists from 9 countries. It encompasses the definition, diagnosis, treatment, and follow-up of the disease, the identification of barriers to healthcare, and proposals to improve the disease care in the region. INTRODUCTION: There is a gap in the understanding of osteoporosis in Latin America. The objective of this work is to state the position of the Latin American Federation of Endocrinology on osteoporosis care in postmenopausal women to better bridge this gap. METHODS: An experts' panel was formed comprising of 11 endocrinologists from 9 countries. A data search was conducted with a conceptual approach and data selection was based on the hierarchy of the EBHC pyramid. Unpublished data was considered for local epidemiological data and expert opinion for the identification of barriers to healthcare. An expert consensus based on the Delphi methodology was carried out. Experts were asked to respond on a 5-point Likert Scale to two provided answers to guiding questions. RESULTS: Consensus was agreed on the answer for the questions with the higher median on the Likert scale and synthetized on 16 statements covering the definition of osteoporosis, diagnostic approach, treatment options, and follow-up. Besides clinical topics, unmet needs in osteoporosis were identified in relation to local epidemiological data, barriers to treatment, and misclassification of programs within health systems. CONCLUSIONS: Through a process based on recognized methodological tools, FELAEN's position on osteoporosis was developed. This made it possible to state an optimum scenario for the care of the disease and helped to identify knowledge gaps. There is great variability in the approach to osteoporosis in Latin America and barriers in all the stages of healthcare persist.

Immune reconstitution in human immunodeficiency virus type 1-infected children with different virological responses to anti-retroviral therapy.

Immune repopulation, despite virological failure, often occurs in children under highly active anti-retroviral therapy (HAART). The aim of this study was to analyse the characteristics of immune repopulation and activation in children with and without virological response to HAART. Fourteen human immunodeficiency virus type 1 (HIV-1)-infected children with suppression of HIV-1 plasma viraemia (virological responders, VR) and 16 virological non-responders (VNR) to therapy were studied at baseline and after approximately 2 years of HAART. During therapy, CD4+ T cells increased in both groups, but were higher in the VR than in the VNR group. All CD4+ T cell subsets (naive, central memory, effector/memory and CD38+) increased significantly in VR children, while there was a significant increase only in naive cells in VNR children. Naive CD8+ T cells and T cell receptor rearrangement excision circles (TREC), an indicator of thymic output, increased in both VR and VNR children. Activated CD8+ CD38+ T cells decreased in VR but remained high in VNR children. Levels of circulating lipopolysaccharide (LPS), an indicator of microbial translocation, further increased in VNR children. In conclusion, HAART induced an increase in naive cells in all children, regardless of their virological response. However, the persistence of viraemia resulted in an impaired expansion of memory CD4+ T cells susceptible to HIV-1 infection, and together with the microbial translocation sustained the persistence of a high level of immune activation.

Effect of Denosumab on Bone Mineral Density and Markers of Bone Turnover among Postmenopausal Women with Osteoporosis.

The aim of this study was to evaluate the effect of denosumab (Dmab) on bone mineral density (BMD) and bone turnover markers after 1 year of treatment. Additionally, the effect of Dmab in bisphosphonate-naïve patients (BP-naïve) compared to patients previously treated with bisphosphonates (BP-prior) was analyzed. This retrospective study included 425 postmenopausal women treated with Dmab for 1 year in clinical practice conditions in specialized centers from Argentina. Participants were also divided according to previous bisphosphonate treatment into BP-naïve and BP-prior. A control group of patients treated with BP not switched to Dmab matched by sex, age, and body mass index was used. Data are expressed as mean ± SEM. After 1 year of treatment with Dmab the bone formation markers total alkaline phosphatase and osteocalcin were significantly decreased (23.36% and 43.97%, resp.), as was the bone resorption marker s-CTX (69.61%). Significant increases in BMD were observed at the lumbar spine, femoral neck, and total hip without differences between BP-naïve and BP-prior. A better BMD response was found in BP-prior group compared with BP treated patients not switched to Dmab. Conclusion. Dmab treatment increased BMD and decreased bone turnover markers in the whole group, with similar response in BP-naïve and BP-prior patients. A better BMD response in BP-prior patients versus BP treated patients not switched to Dmab was observed.

Co-receptor usage of HIV-1 primary isolates, viral burden, and CCR5 genotype in mother-to-child HIV-1 transmission.

OBJECTIVE: To investigate the relationship between CC chemokine receptor 5 (CCR5) genotype, viral load and co-receptor usage of maternal HIV-1 isolates in perinatal HIV-1 transmission. PATIENTS AND METHODS: A total of 181 mothers and infants were studied at the time of delivery. Wild-type (wt) and delta32 CCR5 alleles were determined by means of polymerase chain reaction (PCR). The viral load in maternal plasma samples was determined by a quantitative reverse transcriptase-PCR assay; co-receptor usage of maternal isolates was determined by viral infection in cells stably expressing CCR5 or CXC chemokine receptor 4 (CXCR4) co-receptors. RESULTS: HIV-1 transmission rates in wt/wt and wt/delta32 mothers (14.7 versus 15.8%), and in wt/wt and wt/delta32 infants (14.6 versus 14.3%) were similar. Mothers transmitting infection to wt/delta32 infants had significantly higher HIV-1-RNA levels than those who transmitted infection to wt/wt infants (5.4 versus 4.1 log10 copies/ml, P = 0.03). In wt/wt children there was a positive relationship between transmission rate and maternal viral load over the entire range of HIV-1 values, whereas in wt/delta32 children transmission occurred only at viral loads greater than 4.0 log10 copies/ml. Logistic regression analysis confirmed that the relationship between viral load and transmission varied according to the child's CCR5 genotype (P = 0.035; adjusted for zidovudine prophylaxis and mode of delivery, P = 0.090). Moreover, the majority of wt/wt transmitting mothers had R5-type isolates, whereas none of the wt/delta32 mothers with an R5-type virus transmitted HIV-1 to their wt/delta32 infants. CONCLUSION: Taken together, these findings suggest that CCR5 delta32 heterozygosity exerts a protective effect against perinatal transmission in children exposed to a low maternal viral burden of an R5-type isolate.

Acquired immunodeficiency syndrome-related Kaposi's sarcoma regression after highly active antiretroviral therapy: biologic correlates of clinical outcome.

BACKGROUND: Kaposi's sarcoma (KS) is the most common cancer seen in subjects with acquired immunodeficiency syndrome (AIDS). KS etiology and pathogenesis are still ill defined, and no definite improvement in survival has been obtained with current chemotherapeutic regimens. This open prospective study was aimed at evaluating the clinical response of AIDS-related KS to highly active antiretroviral therapy (HAART), a combination of protease and reverse transcriptase inhibitors, as well as the relationship between clinical response, human immunodeficiency virus type 1 (HIV-1) burden, and antibody titer against human herpesvirus 8 (HHV8) proteins. PATIENTS AND METHODS: Fourteen KS patients were studied; 12 were in the poor-risk group. At given intervals, the patients underwent clinical examination, and their CD4(+) cell counts, plasma HIV-1 RNA levels, and antibody titers to lytic-phase ORF65 and latent-phase HHV8 proteins were determined. RESULTS: When last seen, the overall clinical response rate was 86% (median follow-up, 22 months); 10 complete and two partial responses were achieved, and two patients showed disease progression. All patients with complete or partial response showed a consistent decrease in HIV-1 RNA levels, with a corresponding increase in CD4(+) cell counts; HIV-1 RNA levels in the two progressors remained persistently high, despite a change in HAART. HHV8 ORF65 antibody titers were generally higher in patients with extensive skin or mucosal/visceral involvement versus patients with limited disease; no differences in latent-phase HHV8 antibody titers were observed in relation to tumor burden. CONCLUSION: The findings indicate that antiretroviral therapy with protease inhibitors is effective for AIDS-related KS; the clinical response was correlated with a decrease in plasma HIV-1 RNA levels and an increase in CD4(+) lymphocytes, whereas antibody levels to the lytic-phase HHV8 protein were influenced by the extent of tumor involvement.

Regression of AIDS-related Kaposi's sarcoma following antiretroviral therapy with protease inhibitors: biological correlates of clinical outcome.

The clinical response of AIDS-related Kaposi's sarcoma (KS) to highly active antiretroviral therapy (HAART), a combination of human immunodeficiency virus type 1 (HIV-1) protease and reverse transcriptase inhibitors, was studied in 11 patients, all but one with progressive KS. CD4+ cell counts, plasma HIV-1 RNA levels, and antibody titres to lytic ORF65 and latency-associated human herpes virus type 8 (HHV-8) proteins were determined in sequential samples. Six complete and three partial clinical responses were achieved in a median time of 6 and 3 months, respectively, and confirmed after a median time of 16 months on HAART. 2 patients showed disease progression. A consistent decrease in HIV-1 RNA levels, paralleled by an increase in CD4+ cell counts, was observed in all patients who showed complete or partial clinical response; HIV-1 RNA levels remained persistently high in the two patients who progressed, despite a change in HAART. HHV-8 antibody titres were generally higher in patients with mucosal/visceral involvement compared with patients with limited disease; a decrease in ORF65 antibody titre was significantly associated with a clinical response. These results indicate that HAART is effective for AIDS-related KS; the clinical response correlates with a decrease in plasma HIV-1 RNA levels, an increase in CD4+ lymphocytes, and a decrease in antibodies to ORF65 HHV-8 protein.

Restriction of HIV type 1 infection in macrophages heterozygous for a deletion in the CC-chemokine receptor 5 gene.

Homozygosity for a 32-base pair deletion (delta32) within the CC-chemokine receptor 5 (CCR5) gene confers resistance to infection by R5-type HIV-1 isolates. To ascertain how CCR5delta32 heterozygosity influences the susceptibility of lymphocytes and macrophages to HIV-1 infection, peripheral blood lymphocytes (PBLs) and monocyte-derived macrophages (MDMs) from three HIV-1-uninfected CCR5delta32 heterozygous infants and three HIV-1-uninfected CCR5 wild-type homozygous infants were exposed to two R5-type primary isolates. HIV-1 infection was monitored by DNA-PCR and p24 antigen determination; CCR5 and CCR5delta32 transcripts were quantified by competitive reverse transcription-PCR. Wild-type homozygous MDMs and PBLs and heterozygous PBLs were infected by both viral isolates, albeit with different efficiencies, but heterozygous MDMs showed restriction to HIV-1 infection. Lower levels of CCR5 mRNA and protein expression were found in heterozygous versus wild-type homozygous MDMs and PBLs. Interestingly, wild-type homozygous MDMs showed higher levels of CCR5 mRNA expression compared with wild-type homozygous PBLs, while heterozygous MDMs had lower levels of CCR5 wild-type mRNA and a higher CCR5delta32/CCR5 mRNA ratio compared with heterozygous PBLs. These findings suggest that CCR5delta32 heterozygosity confers a different degree of protection against HIV-1 in PBLs and MDMs, depending on the ratio of wild-type and mutant CCR5 mRNA in the two cell types, and may delay virus spread in the host by preventing infection of monocytes and macrophages.

A clinical evaluation of monoclonal (CA19-9, CA50, CA12-5) and polyclonal (CEA, TPA) antibody-defined antigens for the diagnosis of pancreatic cancer.

We measured in 193 patients, admitted to our wards for symptoms and signs suggestive of pancreatic or digestive malignancy, the serum levels of five tumor-associated antigens (CA 19-9, CA 50, CA 125, TPA, CEA) and we evaluated their diagnostic accuracy both when used alone and in combination. For CA 19-9 and CA 50 a sensitivity for pancreatic cancer as high as 92 and 88%, respectively, and specificity of 91.8% were found. A lower sensitivity vs. pancreatic cancer was found for the other tumor markers, and vs. the other digestive and nondigestive malignancies for all tumor markers (apart for CA 19-9 and CA 50 vs. biliary carcinomas). As for the combined assays, the best figures were found vs. pancreatic cancer for CA 19-9 plus CA 50, CA 50 plus CEA, CA 50 plus CA 125; a sensitivity by far worse vs. the other gastrointestinal cancers was found for all the possible combinations. We conclude that in selected symptomatic patients some tumor-marker determinations can be useful in identifying those with a high probability of harboring a pancreatic cancer, to be further studied or operated upon. The clinical relevance of this in patients already symptomatic is at present unclear.

Enzyme immunoassay for pancreatic lipase: comparison with turbidimetric method in pancreatic diseases.

We report the results of the analytical and clinical evaluation of a specific enzyme immunoassay for determination of human pancreatic lipase, in comparison with a turbidimetric method, in pancreatic pathology. Under standardized conditions of incubation time and temperature we found intraassay coefficient of variation (CV) of 1.3, 3.2, 2.1% at means = 18.7, 43.7, 224 micrograms/L and interassay CV of 2.8, 4.6, 3.0% at means = 19, 42.6, 230 micrograms/L, respectively. In general, a good correlation (r = 0.97) was found between lipase determined as a protein or through its catalytic activity. No significant correlation (r = 0.38) was observed with samples containing low concentration of lipase (up to 18 micrograms/L). We conclude that the turbidimetric method is reliable for routine determinations in the diagnosis of acute pancreatic pathology. However, the better sensitivity of the immunochemical assay should provide additional information for monitoring pancreatic insufficiency.

On-line intracardiac echocardiography alone for Amplatzer Septal Occluder selection and device deployment in adult patients with atrial septal defect.

BACKGROUND: During the last few years, several different devices have been proposed for atrial septal defect (ASD) percutaneous closure. For the Amplatzer Septal Occluder (ASO) device, accurate balloon sizing is considered of paramount importance because the prosthesis waist has to be exactly adjusted to the defect diameter (+/-1 mm). In this study, we aimed to demonstrate the possibility of marked misinterpreting of the actual defect size using the balloon technique in patients with secundum ASD and to evaluate the accuracy of intracardiac echocardiography (ICE) measurements as a new method for selecting the size of ASO device. METHODS: Between February 1999 and December 2000, 166 consecutive adult patients underwent percutaneous transvenous secundum ASD occlusion using the ASO device. In 124 patients (control group), ASD were closed by conventional methods. In 13 patients (pilot group), balloon pulling technique was used in size selection, whereas ICE was used on-line to monitor device placement and off-line to assess its possibilities for accurate quantitative measurements and qualitative evaluation. In 31 patients (study group), ICE was used as the sole imaging tool both for guiding device selection and monitoring the procedure. All patients underwent complete transthoracic echocardiographic study before discharge and during follow-up visits at 3 and 12 months. RESULTS: Successful device implantation was accomplished in 163 of the 166 patients (98.2%). Short-term follow-up results were available in all eligible patients at least 3 months. Complete occlusion was demonstrated in 91.4% and 92.2% of patients in the control and pilot groups, respectively, increasing to 97.3% in the study group (p<0.01 vs. both control and pilot groups). There were no significant differences in mean ASO diameters in the control and pilot groups (20+/-7.7 and 22+/-5.4 mm, respectively), whereas the mean size of the devices used in the study group was significantly larger (27.4+/-6.2 mm, p<0.01 vs. both control and pilot groups). In the pilot group, the underestimation effect of the balloon strategy was evident, with a mean 12.3% larger diameter required on ICE measurements. Moreover, a misalignment between the ASO and the atrial septum was seen on ICE in 9 of 13 patients of the pilot group, whereas good apposition of the ASO on the septum secundum was seen in all patients of the study group. CONCLUSION: ICE is a safe and effective method for selecting ASO size and continuous monitoring of the procedure. In contrast to the previously reported implantation procedure (device-to-defect ratio 1:1), a device 10-20% larger than invasively measured stretched defect diameter should be chosen and implanted on the basis of the ICE data.