Dermoscopic Changes in Melanocytic Lesions in 368 Patients With Atypical Nevus Syndrome and Their Association With Melanoma Incidence: A Cohort Study. / Cambios en la dermatoscopia digital en lesiones melanocíticas en 368 pacientes con diagnóstico de síndrome de nevus atípicos y su asociación con el desarrollo de melanoma: estudio de cohorte.

BACKGROUND AND OBJECTIVE: Atypical nevus syndrome has been described as one of the main risk factors for melanoma. The aim of this study was to analyze dermoscopic changes observed in melanocytic lesions over a follow-up period of 5 years in patients with atypical nevus syndrome. MATERIAL AND METHODS: We conducted a retrospective follow-up study of a cohort of patients seen at a specialized skin cancer and digital body mapping clinic in Medellin, Colombia, between January 2017 and December 2022. We analyzed the dermoscopic changes observed during this period and explored their association with newly diagnosed melanoma. RESULTS: A total of 368 patients (187 women) with a median (interquartile range) age of 43 (37-51) years were included. The dermoscopic features observed at 5 years were an atypical network (222 patients, 60.3%), asymmetric globules (163, 44.2%), white-gray regression areas (105, 28.5%), lesion regression (72, 19.5%), a negative pigment network (59, 16%), asymmetric eccentric pigmentation (28, 7.6%), asymmetric projections (21, 5.7%), and asymmetric vascular patterns (8, 2.1%). Melanoma was diagnosed in 12.2% of patients during follow-up. Features significantly associated with a shorter time to melanoma onset were grayish-white areas (P <.001), asymmetric globules (P=.011), asymmetric eccentric pigmentation (P=.047), and a negative pigment network (P=.001). CONCLUSIONS: The main dermoscopic features of melanocytic lesions in patients with atypical nevus syndrome associated with progression to melanoma were grayish-white areas, asymmetric globules, asymmetric spots, and a negative pigment network.

[Translated article] Dermoscopic Changes in Melanocytic Lesions in 368 Patients With Atypical Nevus Syndrome and Their Association With Melanoma Incidence: A Cohort Study.

BACKGROUND AND OBJECTIVE: Atypical nevus syndrome has been described as one of the main risk factors for melanoma. The aim of this study was to analyze dermoscopic changes observed in melanocytic lesions over a follow-up period of 5 years in patients with atypical nevus syndrome. MATERIAL AND METHODS: We conducted a retrospective follow-up study of a cohort of patients seen at a specialized skin cancer and digital body mapping clinic in Medellin, Colombia, between January 2017 and December 2022. We analyzed the dermoscopic changes observed during this period and explored their association with newly diagnosed melanoma. RESULTS: A total of 368 patients (187 women) with a median (interquartile range) age of 43 (37-51) years were included. The dermoscopic features observed at 5 years were an atypical network (222 patients, 60.3%), asymmetric globules (163, 44.2%), white-gray regression areas (105, 28.5%), lesion regression (72, 19.5%), a negative pigment network (59, 16%), asymmetric eccentric pigmentation (28, 7.6%), asymmetric projections (21, 5.7%), and asymmetric vascular patterns (8, 2.1%). Melanoma was diagnosed in 12.2% of patients during follow-up. Features significantly associated with a shorter time to melanoma onset were grayish-white areas (P<.001), asymmetric globules (P=.011), asymmetric eccentric pigmentation (P=.047), and a negative pigment network (P=.001). CONCLUSIONS: The main dermoscopic features of melanocytic lesions in patients with atypical nevus syndrome associated with progression to melanoma were grayish-white areas, asymmetric globules, asymmetric spots, and a negative pigment network.

Correlation of the virological response to short-term maraviroc monotherapy with standard and deep-sequencing-based genotypic tropism prediction methods.

Genotypic tropism testing methods are emerging as the first step before prescription of the CCR5 antagonist maraviroc (MVC) to HIV-infected patients in Europe. Studies validating genotypic tests have included other active drugs that could have potentially convoluted the effects of MVC. The maraviroc clinical test (MCT) is an in vivo drug sensitivity test based on the virological response to a short-term exposure to MVC monotherapy. Thus, our aim was to compare the results of genotypic tropism testing methods with the short-term virological response to MVC monotherapy. A virological response in the MCT was defined as a ≥ 1-log(10) decrease in HIV RNA or undetectability after 8 days of drug exposure. Seventy-three patients undergoing the MCT were included in this study. We used both standard genotypic methods (n = 73) and deep sequencing (n = 27) on MCT samples at baseline. For the standard methods, the most widely used genotypic algorithms for analyzing the V3 loop sequence, geno2pheno and PSSM, were used. For deep sequencing, the geno2pheno algorithm was used with a false-positive rate cutoff of 3.5. The discordance rates between the standard genotypic methods and the virological response were approximately 20% (including mostly patients without a virological response). Interestingly, these discordance rates were similar to that obtained from deep sequencing (18.5%). The discordance rates between the genotypic methods (tropism assays predictive of the use of the CCR5 coreceptor) and the MCT (in vivo MVC sensitivity assay) indicate that the algorithms used by genotypic methods are still not sufficiently optimized.

Cambios en la dermatoscopia digital en lesiones melanocíticas en 368 pacientes con diagnóstico de síndrome de nevus atípicos y su asociación con el desarrollo de melanoma: estudio de cohorte / Dermoscopic Changes in Melanocytic Lesions in 368 Patients With Atypical Nevus Syndrome and Their Association With Melanoma Incidence: A Cohort Study

Antecedentes y objetivo El síndrome de nevus atípico se ha considerado uno de los factores más importantes para el desarrollo de melanoma. El objetivo de este estudio fue describir los cambios dermatoscópicos de las lesiones melanocíticas en pacientes con diagnóstico de síndrome de nevus atípicos, durante el seguimiento digital en 5 años. Material y métodos Se realizó un estudio retrospectivo de seguimiento a una cohorte de pacientes atendidos en un consultorio particular, especializado en cáncer de piel y mapeo digital corporal, localizado en Medellín (Colombia), entre enero de 2017 y diciembre de 2022. Se analizaron las características dermatoscópicas encontradas y su relación con el diagnóstico de un melanoma. Resultados Se incluyeron 368 pacientes, con una mediana de edad de 43 años RIQ (37-51) de los cuales,187 fueron mujeres. Al finalizar el seguimiento, 222 (60,3%) presentaron red atípica, 163 (44,2%) glóbulos asimétricos, 105 (28,5%) regresión blanco gris, 72 (19,5%) regresión de la lesión, 59 (16%) retículo invertido, 28 (7,6%) pigmento excéntrico asimétrico, 21 (5,7%) proyecciones asimétricas y 8 (2,1%) asimetría en el patrón vascular. A los 60 meses de seguimiento a un 12,2% se les diagnosticó un melanoma. Las áreas blanco-grisáceas, los glóbulos asimétricos, el pigmento excéntrico asimétrico y el retículo invertido fueron las estructuras dermatoscópicas que se relacionaron significativamente con un tiempo menor para la presentación de melanoma (p<0,001, p=0,011, p=0,047 y p=0,001, respectivamente). Conclusiones En conclusión, se encontró que las principales características dermatoscópicas de las lesiones melanocíticas en pacientes con nevus displásicos relacionadas con la progresión a melanoma fueron la aparición de áreas blanco-grisáceas, los glóbulos asimétricos, las manchas asimétricas y el retículo invertido (AU)

Background and objective Atypical nevus syndrome has been described as one of the main risk factors for melanoma. The aim of this study was to analyze dermoscopic changes observed in melanocytic lesions over a follow-up period of 5 years in patients with atypical nevus syndrome. Material and methods We conducted a retrospective follow-up study of a cohort of patients seen at a specialized skin cancer and digital body mapping clinic in Medellin, Colombia, between January 2017 and December 2022. We analyzed the dermoscopic changes observed during this period and explored their association with newly diagnosed melanoma. Results A total of 368 patients (187 women) with a median (interquartile range) age of 43 (37-51) years were included. The dermoscopic features observed at 5 years were an atypical network (222 patients, 60.3%), asymmetric globules (163, 44.2%), white-gray regression areas (105, 28.5%), lesion regression (72, 19.5%), a negative pigment network (59, 16%), asymmetric eccentric pigmentation (28, 7.6%), asymmetric projections (21, 5.7%), and asymmetric vascular patterns (8, 2.1%). Melanoma was diagnosed in 12.2% of patients during follow-up. Features significantly associated with a shorter time to melanoma onset were grayish-white areas (P <.001), asymmetric globules (P=.011), asymmetric eccentric pigmentation (P=.047), and a negative pigment network (P=.001). Conclusions The main dermoscopic features of melanocytic lesions in patients with atypical nevus syndrome associated with progression to melanoma were grayish-white areas, asymmetric globules, asymmetric spots, and a negative pigment network (AU)

[Translated article] Dermoscopic Changes in Melanocytic Lesions in 368 Patients With Atypical Nevus Syndrome and Their Association With Melanoma Incidence: A Cohort Study / Cambios en la dermatoscopia digital en lesiones melanocíticas en 368 pacientes con diagnóstico de síndrome de nevus atípicos y su asociación con el desarrollo de melanoma: estudio de cohorte

Background and objective Atypical nevus syndrome has been described as one of the main risk factors for melanoma. The aim of this study was to analyze dermoscopic changes observed in melanocytic lesions over a follow-up period of 5 years in patients with atypical nevus syndrome. Material and methods We conducted a retrospective follow-up study of a cohort of patients seen at a specialized skin cancer and digital body mapping clinic in Medellin, Colombia, between January 2017 and December 2022. We analyzed the dermoscopic changes observed during this period and explored their association with newly diagnosed melanoma. Results A total of 368 patients (187 women) with a median (interquartile range) age of 43 (37-51) years were included. The dermoscopic features observed at 5 years were an atypical network (222 patients, 60.3%), asymmetric globules (163, 44.2%), white-gray regression areas (105, 28.5%), lesion regression (72, 19.5%), a negative pigment network (59, 16%), asymmetric eccentric pigmentation (28, 7.6%), asymmetric projections (21, 5.7%), and asymmetric vascular patterns (8, 2.1%). Melanoma was diagnosed in 12.2% of patients during follow-up. Features significantly associated with a shorter time to melanoma onset were grayish-white areas (P <.001), asymmetric globules (P=.011), asymmetric eccentric pigmentation (P=.047), and a negative pigment network (P=.001). Conclusions The main dermoscopic features of melanocytic lesions in patients with atypical nevus syndrome associated with progression to melanoma were grayish-white areas, asymmetric globules, asymmetric spots, and a negative pigment network (AU)

Antecedentes y objetivo El síndrome de nevus atípico se ha considerado uno de los factores más importantes para el desarrollo de melanoma. El objetivo de este estudio fue describir los cambios dermatoscópicos de las lesiones melanocíticas en pacientes con diagnóstico de síndrome de nevus atípicos, durante el seguimiento digital en 5 años. Material y métodos Se realizó un estudio retrospectivo de seguimiento a una cohorte de pacientes atendidos en un consultorio particular, especializado en cáncer de piel y mapeo digital corporal, localizado en Medellín (Colombia), entre enero de 2017 y diciembre de 2022. Se analizaron las características dermatoscópicas encontradas y su relación con el diagnóstico de un melanoma. Resultados Se incluyeron 368 pacientes, con una mediana de edad de 43 años RIQ (37-51) de los cuales,187 fueron mujeres. Al finalizar el seguimiento, 222 (60,3%) presentaron red atípica, 163 (44,2%) glóbulos asimétricos, 105 (28,5%) regresión blanco gris, 72 (19,5%) regresión de la lesión, 59 (16%) retículo invertido, 28 (7,6%) pigmento excéntrico asimétrico, 21 (5,7%) proyecciones asimétricas y 8 (2,1%) asimetría en el patrón vascular. A los 60 meses de seguimiento a un 12,2% se les diagnosticó un melanoma. Las áreas blanco-grisáceas, los glóbulos asimétricos, el pigmento excéntrico asimétrico y el retículo invertido fueron las estructuras dermatoscópicas que se relacionaron significativamente con un tiempo menor para la presentación de melanoma (p<0,001, p=0,011, p=0,047 y p=0,001, respectivamente). Conclusiones En conclusión, se encontró que las principales características dermatoscópicas de las lesiones melanocíticas en pacientes con nevus displásicos relacionadas con la progresión a melanoma fueron la aparición de áreas blanco-grisáceas, los glóbulos asimétricos, las manchas asimétricas y el retículo invertido (AU)

Glycogen synthase kinase-3 is involved in the regulation of the cell cycle in cerebellar granule cells.

Recent studies have demonstrated that neuronal reentry in the cell cycle and specifically the expression of the transcription factor E2F-1, constitutes a pathway that may be involved in neuronal apoptosis after serum and potassium withdrawal. Other enzymes such as glycogen synthase kinase-3beta (GSK-3beta) are also involved in this apoptotic stimulus, and thus in the process of neuronal cell death. Primary cerebellar granule cells (CGNs) were used in this study to determine whether pharmacological inhibition of GSK-3beta is involved in neuronal modulation of the cell cycle, and specifically in the regulation of E2F-1 and retinoblastoma protein (Rb). CGNs showed a dramatic increase in GSK-3beta activity after 2h of serum and potassium deprivation. Immunoblot and activity assays revealed that lithium and SB415286 inhibit fully the activation of GSK-3beta and attenuate the expression of cyclin D, cyclin E, pRb phosphorylation and the transcription factor E2F-1. These data were confirmed using AR-014418, a selective GSK-3beta inhibitor that prevents the expression of cell-cycle proteins. Our data indicate that GSK-3beta inhibition regulates, in part, the cell cycle in CGNs by inhibiting Rb phosphorylation and thus inhibiting E2F-1 activity. However, the selective inhibition of GSK-3beta with AR-A014418 had not effect on cell viability or apoptosis mediated by S/K withdrawal. Furthermore, our results suggest that selective GSK-3beta inhibition is not sufficient to protect against apoptosis in this S/K withdrawal model, indicating that Li(+) and SB415286 neuroprotective effects are mediated by the inhibition of additional targets to GSK3beta. Therefore, there is a connection between cell cycle and GSK-3beta activation and that these, along with other mechanisms, are involved in the molecular paths leading to the apoptotic process of rat CGNs triggered by S/K withdrawal.

Influence of hepatitis C and hepatitis G virus co-infection on viral and cellular dynamics in patients infected with human immunodeficiency virus following interruption of highly active anti-retroviral therapy.

This study describes the influence of hepatitis C virus (HCV) and hepatitis G virus (HGV) co-infection on CD4 cell count decline and plasma human immunodeficiency virus (HIV) viral load in HIV-infected patients during a 1-year period following interruption of highly active anti-retroviral therapy (HAART) guided by CD4 count. CD4 cell count decline and plasma HIV viral load did not differ between HIV mono-infected patients and those patients co-infected with HCV and HGV. HCV genotype 1 had no apparent influence on the cellular and viral dynamics in HIV-infected patients compared with other HCV genotypes, although the unbalanced groups make larger studies desirable.

HIV-1 infection among non-intravenous drug user female prostitutes in Spain. No evidence of evolution to pattern II.

OBJECTIVES: To assess the prevalence of HIV-1 infection among non-intravenous drug user (IVDU) female prostitutes in Spain and to determine risk factors for HIV-1 infection in this population. DESIGN: Cross-sectional seroepidemiological study of 519 non-IVDU prostitutes. SETTING: Four university hospitals. METHODS: All participants completed a questionnaire and provided a serum sample. Serum samples were tested for antibodies against HIV-1, hepatitis C virus (HCV) and Treponema pallidum. RESULTS: Twelve out of the 519 (2.31%) participants were HIV-1-seropositive. HIV-1 infection was associated with the presence of both HCV and T. pallidum antibodies, multiple sex partners, longer history of prostitution, history of genital ulcers and anal intercourse. Condom use was associated with HIV-1 seronegativity. CONCLUSIONS: The prevalence of HIV-1 infection in non-IVDU prostitutes in Spain remains relatively low. Risk increases with a higher rate of sexual exposure and practices such as anal intercourse and unprotected coitus.

PIP: HIV-1 has been spreading according to pattern 1 in Europe and North America. In Kenya and Nigeria, where pattern 2 transmission is established, large increases in the prevalence of antibodies to HIV-1 in non-intravenous drug using (IVDU) female prostitutes were documented before HIV-1 disseminated into the general population. 519 non-IVDU female prostitutes in Spain were studied to assess the prevalence of HIV-1 infection among them and to determine the risk factors for infection in the population. The cross-sectional seroepidemiological study was conducted in four university hospitals in Andalusia, southern Spain. Subjects were of mean age 30 years with range 18-55 years; had an average 59 sex partners/month with range 1-600; and had worked as a prostitute for an average 50 months with range 2-420 months. Respondents answered questionnaires and provided serum samples for analysis. 12/519 or 2.31% were seropositive for HIV-1. Infection was associated with the presence of antibodies to hepatitis C and Treponema pallidum, multiple sex partners, longer history f prostitution, and history of genital ulcers and anal intercourse. Condom use was associated with HIV-1 seronegativity. In sum, relatively low prevalence of HIV-1 infection was found among these sex workers, thereby offering no evidence of a shift from pattern 1 to pattern 2 transmission in the broader population.

A rapid enzyme-immunoassay for the detection of ciguatoxin in contaminated fish tissues.

An enzyme-immunoassay procedure for the detection of ciguatoxin has been developed using the sheep anti-ciguatoxin serum described earlier in the radioimmunoassay method for ciguatoxin. In the enzyme-immunoassay procedure, the sheep anti-ciguatoxin was coupled to horseradish peroxidase. Analyses of fish tissues showed that the enzyme-immunoassay procedure distinguished between clinically documented toxic and nontoxic tissues (P less than 0.001). Comparisons of the enzyme-immunoassay method with the radioimmunoassay for ciguatoxin and with a mouse bioassay demonstrated significant associations (P less than 0.001 and P less than 0.01, respectively). Preliminary studies showed that purified ciguatoxin inhibited the binding of sheep anti-ciguatoxin horseradish peroxidase to toxic fish tissues. Results suggest that the enzyme-immunoassay procedure may be valuable for routine direct assessment of ciguatoxin in fish tissues because of its practicality, sensitivity and specificity.

Comparison of three different assays for the assessment of ciguatoxin in fish tissues: radioimmunoassay, mouse bioassay and in vitro guinea pig atrium assay.

Moderate correlation was shown between the following tests: RIA: mouse bioassay (r = 0.58); RIA: guinea pig atrium assay (r = 0.62); guinea pig atrium assay: mouse bioassay (r = 0.62). All three assay procedures showed good correlation when ciguatoxin was present in tissues in high concentrations. The results also suggest that more than one structurally related toxin may be present in the fish tissues.

[Characteristics of metastatic prostate cancer occurring in patients under 50 years of age]. / Patrón de presentación del cáncer de próstata avanzado en pacientes menores de cincuenta años.

OBJECTIVE: To identify the clinical features, diagnostic approach, and treatment of metastatic prostate cancer in young adult patients. METHODS: A retrospective review was made of the clinical histories of patients under 50 years of age diagnosed with prostate cancer at the urology department of the National Institute for Neoplastic Diseases from 1952 to 2005. Demographic characteristics and data on history, symptoms, diagnostic procedures, treatment, and disease course were collected. Data were statistically analyzed and compared to information obtained from a literature search. RESULTS: There were 69 patients aged less than 50 years who had been diagnosed with prostate cancer, 60% of whom had metastatic tumors. Mean patient age was 45.5 years, with a lower range of 29. All patients reported bone pain, associated to other signs and symptoms such as spinal cord compression (19.5%), lower limb edema (17%), peripheral adenopathies (36.5%), and abdominal tumor (2.4%). All patients had bone metastases, of which 14.6% were in solid organs (lung and liver), 48.7% in retroperitoneum, and 7.3% in mediastinum. Initially, three patients were diagnosed a lymphoproliferative syndrome, one patient a retroperitoneal tumor of unknown etiology, and four patients a metastasis from an unknown primary tumor. Mean prostate-specific antigen (PSA) level was 795 ng/mL (3-6500). All pathologies were reported as poorly differentiated or undifferentiated. Mean survival was 16.1 months (1-84), and all patients died due to disease progression. CONCLUSIONS: Advanced prostate cancer is an uncommon condition in young adults. Its clinical presentation is atypical, as metastases may mimic other diseases. The course of disease is indolent, and prognosis is poor. In patients with risk factors, PSA testing should be started before 50 years of age.

Analysis of quasispecies in the viral 5' untranslated region of hepatitis C virus to evaluate ribavirin mutagenic effect in patients receiving ribavirin and interferon-alfa.

In the study presented here the ribavirin mutagenic effect was investigated by analyzing quasispecies in the viral 5' untranslated region of hepatitis C virus in six patients with chronic infection who started interpheron-alpha and ribavirin therapy. A remarkable mutation rate during treatment was found in only one individual. This patient had a sustained response and harbored a type 3a virus strain. The different mutated clones in this patient demonstrated no apparent close relationship that could suggest lack of selection pressure by ribavirin. The mutations were located within the loops of subdomains IIIb and IIId of the internal ribosomal entry site. This is an interesting initial finding that needs to be substantiated in a larger trial.

A potent naturally occurring low-molecular weight blastogenic inhibitory factor from edible black tree fungus.

Crude dialyzable extracts of Auricularia polytricha (black tree fungus) when added to lymphoprep-isolated blood mononuclear cells (PBL) stimulated with mitogens (PHA and PWM) showed significant inhibition of 3H-thymidine (3H-TdR) incorporation in vitro. Similar extracts of Agaricus biporus and Cortinellus shiitake demonstrated essentially no suppression of 3H-TdR uptake by PBL cells stimulated with PHA or PWM. A 50 micrograms/well (200 microliter) concentration of A. polytricha reduced 3H-TdR uptake of PHA stimulated PBL cells from different donors by 65.4 to 99.8% and similarly reduced 3H-TdR uptake of PWM stimulated PBL cells by 89.6 to 99.9%. Viability examination of PBL cells in RPMI medium with A. polytricha extract alone, mitogens alone, and mixtures of mitogens and extract for 72 hr at 37 degrees C showed per cent survivals as follows: medium alone, 93%; PWM, 91%; PHA, 77%; BTF extract (200 micrograms/ml), 57%; PWM + BTF extract, 47%, and PHA + BTF extract, 39%. Data presented show that Auricularia polytricha contained a low dalton potent blastogenic inhibitory factor(s).

Presence of prostaglandins (PGs) in Tetrahymena pyriformis, GL and the effect of aspirin.

Tetrahymena pyriformis GL appears to require prostaglandins, either B, E or F series for growth, as demonstrated by the deleterious effect of aspirin. The latter inhibits prostaglandin synthetase (cyclooxygenase). Aspirin inhibited 50% growth of a 24 hr culture of T. pyriformis at a dose of approximately 200 micrograms/ml and completely inhibited at 600 micrograms/ml. Extraction with acid ethyl acetate: isopropanol solvent of 2.8 x 10(8) cells yielded 41.3 mg of lipid of which 62.8% and 34.5% were PGE2 and PGB, respectively. It is suggested that PGs are important for the growth of T. pyriformis and that the organism may be a useful source of natural PGs. Additionally, T. pyriformis may be useful in studies of the PGs pathway.

Effect of levamisole on aggregation of platelets stimulated with compounds associated with the prostaglandin synthetic pathway.

Levamisole, L-2,3,5,6-tetrahydro-6-phenylimidazo-(2,1-b)-thiazole-hydrocholoride at various concentrations (2.5 to 40 microgram) added to platelet rich plasma inhibited aggregation of platelets. The 50% inhibition concentrations (IC50) of levamisole in platelet aggregation induced by hydrogen peroixde (9.4 x 10(-1) mM), epinephrine (1.0 x 10(-1) micrometer), endoperoxide-analog (2.9 x 10(-1) micrometer) and arachidonic acid (3.3 micrometer) were 11.0, 8.0, 11.5 and 16.0 microgram/test, respectively. It is suggested that levamisole like imidazole inhibit platelet aggregation and this factor should be considered in the administration of levamisole, especially in cardiovascular diseases.

Hepatitis C virus infection among sexually promiscuous groups and the heterosexual partners of hepatitis C virus infected index cases.

To define the role of sexual transmission in the spread of hepatitis C virus (HCV) infection, a seroprevalence study of antibodies against HCV was performed in populations at high risk for sexually transmitted diseases. Subjects included 310 female prostitutes, 88 clients of prostitutes, 168 homosexual men and 147 stable heterosexual partners of index cases reactive for anti-HCV (98 of whom were partners of drug addicts coinfected with HCV and human immunodeficiency virus [HIV]). All subjects denied prior transfusion or intravenous drug use. Controls were 400 voluntary blood donors selected randomly from first-time donors. The prevalence of anti-HCV by enzyme immunoassay, confirmed by a second-generation recombinant immunoblot assay, was 6.4% in prostitutes, 6.8% in clients of prostitutes, 4.2% in homosexual men, 7.4% in heterosexual partners of index cases and 1.2% in random donors. However, the anti-HCV prevalence in stable heterosexual partners of HCV-positive/HIV-positive index cases was 2.2 times higher than in stable heterosexual partners of index cases reactive for anti-HCV only (9.2% vs. 4.1%), and sexual partners of index cases coinfected with HCV and HIV were almost three times more likely to be infected with HIV than with HCV (25.5% vs. 9.2%). These data suggest that HCV infection may be sexually transmitted but with low efficiency and that this efficiency could be increased in the presence of coexistent HIV infection in the index case.

HIV-1 plasma viremia not increased in patients receiving highly active antiretroviral therapy after influenza vaccination.

The effect of vaccinating patients with sustained undetectable HIV-1 viremia (VL) achieved with highly active antiretroviral therapy was prospectively investigated. During the 1998 influenza immunization period, 39 HIV-1-infected patients who showed a VL<20 copies/ml for at least 6 months before the study entry date were vaccinated for influenza. Twenty-two vaccinees were immunized at entry. Seventeen controls were followed for 4 weeks after entry, crossing over then to the vaccination group. The proportion of patients with undetectable VL was not significantly different between the vaccination and control groups 2 and 4 weeks after entry. Therefore, influenza immunization of patients with undetectable viremia achieved with highly active antiretroviral therapy does not seem to affect VL.

Minimal liver injury in chronic hepatitis C virus infection is associated with low levels of soluble TNF-alpha/Fas receptors and acquisition in childhood.

BACKGROUND/AIMS: The rate of progression to cirrhosis of chronic hepatitis C might be related to an upregulation of TNF-alpha/Fas pathways. METHODS: The serum levels of soluble TNF-alpha type II receptor (sTNFr-II) and soluble Fas antigen (sFas) were analyzed in patients with different histological outcomes of chronic parenterally acquired HCV infection of similar duration. RESULTS: One hundred and forty-five HCV-infected patients had a known duration of infection. Twelve (8.3%) patients had minimal changes and were assigned to the case group. The control group was selected from the 24 (17%) patients with cirrhosis and the 54 (37%) with chronic active hepatitis (CAH). Two controls, one with CAH and one with cirrhosis, were paired with the cases following these criteria: duration of infection, transmission route and sex. The proportions of genotype 1b and HCV RNA serum levels were similar among the groups. The median serum levels of sTNFr-II and sFas were significantly lower in the case group than in the control groups. The cases were significantly younger when they became infected than the control groups. Indeed, most cases were infected within the first 10 years of life. sTNFr-II and age at infection were independently associated with the minimal injury case group. When sTNFr-II was excluded from the logistic regression model, sFas and age at infection were independently associated with the case group. CONCLUSION: The rate of progression of parenterally acquired chronic hepatitis C to end-stage liver disease might be related to an upregulation of the TNF-alpha/Fas pathways and an age-dependent host response.

Unexpected high prevalence of hepatitis C virus genotype 4 in Southern Spain.

BACKGROUND/AIMS: A unusually high rate of HCV-infected individuals in whom the HCV genotype cannot be ascertained by means of single PCR and LIPA procedures has recently been reported in our area. The aim of the present study was to investigate the epidemiological, clinical and molecular characteristics of these patients. METHODS: Cross-sectional study. Eighty anti-HCV-positive patients with chronic liver disease, 45 (56.25%) of them intravenous drug users, were included. HCV genotyping was carried out in all patients using commercial single PCR and LIPA procedures. Samples where no HCV RNA amplification and/or indeterminate HCV genotype were found were also tested by means of a nested PCR. HCV viral load was measured in all patients. RESULTS: HCV genotyping was not achieved in 23 (28.75%) individuals. No amplification of HCV RNA was found in 19 of them, and in four other cases the LIPA procedure did not allow identification of a distinct HCV genotype. After the use of nested PCR+LIPA, it was found that the HCV genotype 4 was found in 11 of those 23 individuals (47.82%). Ten of these 11 HCV genotype 4-harboring individuals were intravenous drug users. The HCV viral load was lower in HCV genotype 4-harboring individuals than in those whom the genotypes 1, 2 or 3 were found (p<0.001). CONCLUSIONS: A high rate of HCV genotype 4-harboring cases has been found among HCV-infected individuals in Southern Spain. Had only single PCR been used, these individuals could have been wrongly regarded as non-viremic.