New magnetostratigraphic evidence for the age of Acheulean tools at the archaeo-palaeontological site "Solana del Zamborino" (Guadix - Baza Basin, S Spain).

The sedimentary record in the Guadix-Baza Basin (southern Spain) has proved to be a great source of information for the Miocene through the Pleistocene periods, due to the abundant faunal remains preserved, in some cases associated with lithic tools. The Solana del Zamborino (SZ) section has been the subject of controversy ever since a magnetostratigraphic analysis resulted in an age of 750-770 Kyr for Acheulean tools, a chronology significantly older than the ~600 Kyr established chronology for the first Acheulean record in Europe. Although recent findings at the "Barranc de la Boella" site (north-east of the Iberian Peninsula) seem to indicate that an earlier introduction of such technique in Europe around 0.96-0.781 Ma is possible, the precise age of the classical site at SZ is still controversial. The aim of this paper is to constrain the chronology of the site by developing a longer magnetostratigraphic record. For this purpose, we carried out an exhaustive sampling in a new succession at SZ. Our results provide a ~65 m magnetostratigraphic record in which 4 magnetozones of normal polarity are found. Our new magnetostratigraphic data suggest an age range between 300-480 Kyr for the lithic tools, closer to the age of traditional Acheulean sites in Europe.

Polymorphism of the human immunodeficiency virus type 2 (HIV-2) protease gene and selection of drug resistance mutations in HIV-2-infected patients treated with protease inhibitors.

We described the baseline polymorphism of the human immunodeficiency virus type 2 (HIV-2) protease gene from 94 treatment-naive patients and the longitudinal follow-up of 17 protease inhibitor-treated patients. Compared to the HIV-2 consensus sequences, baseline polymorphism involved 47 positions. Substitutions selected under treatment were observed at positions corresponding to HIV-1 resistance mutations as well as at positions of currently unknown impact on HIV-1.

[New strategy of actuation in central venous catheter and its influence in infection]. / Nueva estrategia de actuación en los accesos venosos centrales y su influencia en bacteriemias.

The authors inquire if in an educational process and a change in the management for the central venous catheters, have any effect in the decrease of the catheter-related infection (CRI). The strategy consist on doing a new protocol and its communication to the professional people twice per year. A population descriptive analysis is done with medians and description of the etiology. The percentages of CRI are compared between controls periods of one year and intervention periods of one year as well, using association measurements. A total number of 31 CRI's were diagnosed, 19 in the control process and 12 in the intervention process with a results of 8.17 and 4.29 per thousand days of central venous catheter (OR = 0.52; IC = 95%, 0.25 -1.03). In no case was death related with the CRI. The new strategy of handling the central veins access, based on the implications of the assistant staff, reduce the risk of CRI

Immunoblot profile as predictor of toxoplasmic encephalitis in patients infected with human immunodeficiency virus.

In order to define more accurately human immunodeficiency virus-infected patients at risk of developing toxoplasmic encephalitis (TE), we assessed the prognostic significance of the anti-Toxoplasma gondii immunoglobulin G (IgG) immunoblot profile, in addition to AIDS stage, a CD4(+) cell count <50/mm(3), and an antibody titer > or =150 IU/ml, in patients with CD4 cell counts <200/mm(3) and seropositive for T. gondii. Baseline serum samples from 152 patients included in the placebo arm of the ANRS 005-ACTG 154 trial (pyrimethamine versus placebo) were used. The IgG immunoblot profile was determined using a Toxoplasma lysate and read using the Kodak Digital Science 1D image analysis software. Mean follow-up was 15.1 months, and the 1-year incidence of TE was 15.9%. The cumulative probability of TE varied according to the type and number of anti-T. gondii IgG bands and reached 65% at 12 months for patients with IgG bands of 25 and 22 kDa. In a Cox model adjusted for age, gender, Centers for Disease Control and Prevention (CDC) clinical stage, and CD4 and CD8 cell counts, the incidence of TE was higher when the IgG 22-kDa band (hazard ratio [HR] = 5.4; P < 0.001), the IgG 25-kDa band (HR = 4.7; P < 0.001), or the IgG 69-kDa band (HR = 3.4; P < 0.001) was present and was higher for patients at CDC stage C (HR = 4.9; P < 0.001). T. gondii antibody titer and CD4 cell count were not predictive of TE. Thus, detection of IgG bands of 25, 22, and/or 69 kDa may be helpful for deciding when primary prophylaxis for TE should be started or discontinued, especially in the era of highly active antiretroviral therapy.

Human papillomavirus (HPV) DNA in penile carcinomas in Argentina: analysis of primary tumors and lymph nodes.

Among sexually transmitted diseases, infection by human papillomavirus (HPV) has become one of the most important. On the other hand, though epidemiological data show that some HPV types are closely associated with cervical cancer, few reports have been found with reference to penile carcinoma because of its rare occurrence. The aim of this study was to investigate the relationship between HPV infection and penile cancer in Argentina. A retrospective study was carried out on 38 white men with penile squamous-cell carcinoma. Sixty-five archival fixed biopsies taken from 34 primary penile tumors, 25 nodal metastases, 1 skin "satellite" metastasis and 5 histologically normal lymph nodes were used as specimens. HPV detection and typing were carried out by the polymerase chain reaction (PCR) using generic primers, combined with single-stranded conformational polymorphism (SSCP) analysis. HPV DNA was found in 71% patients, corresponding 81% of them to "high risk" types, with predominance of HPV 18. Both primary tumors and metastases showed concordance of HPV occurrence and type in both lesions. In 3 patients, HPV 16 was detected not only in primary tumors and metastases, but also in histologically normal lymph nodes. Our data indicate that most penile carcinomas in Argentine patients are etiologically related to HPV, especially to "high risk" genital types. The agreement in HPV detection between primary tumors and metastases suggests a potential viral role in tumor progression. HPV detection in otherwise histologically normal lymph nodes might be useful as early marker of a metastatic process.

Response at three months is a good predictive factor for newly diagnosed chronic myeloid leukemia patients treated by recombinant interferon-alpha.

In a single institution, we have used recombinant interferon- (IFN-) to treat 116 newly diagnosed Philadelphia-positive (Ph+) chronic myeloid leukemia (CML) patients and analyzed the predictive factors for response and survival. The patients whose median age was 50.3 years (range, 9 to 70) were administered IFN- (5 million units/m2/d) subcutaneously. The IFN- dose was subsequently adjusted to maintain the white blood cell and platelet counts between 1.5 and 5 x 10(9)/L, 50 and 100 x 10(9)/L, respectively. At diagnosis, the Sokal score was used to classify the patients into three groups: low (n = 57), intermediate (n = 42), and high risk (n = 16). A complete hematological response (CHR) was achieved in 93 cases (80.2%). Of the 116 patients, 113 were available for cytogenetic evaluation. Fifty patients (43%) achieved a major cytogenetic response (MCR) (=65% marrow Ph- cells), 37 of them having a complete cytogenetic response (CCR). The estimated 5-year survival of the 116 patients was 68% +/- 11% (95% confidence interval [CI]) with a median follow-up of 42 months (range, 3 to 114) and 85% +/- 11% (95% CI) with a median follow-up of 30.9 (range, 3 to 111) when patients were censored at the time of transplantation. Event-free survival at 5 years (adding death and transplant as event) was 46% +/- 11% (95% CI). Using proportional hazards regression to study time-dependent variables, we confirmed that the most significant factor associated with survival was the cytogenetic response (MCR or CCR) (P <.0001). This factor was independent compared with the Sokal score and baseline variables used to calculate the Sokal score. Moreover, using either univariate or multivariate analysis, the achievement of CHR within 3 months was strongly correlated with MCR (P <.0001). Minimum cytogenetic response (mCR, ie, at least 5% of Ph- metaphases) at 3 months was also a significant predictive factor for MCR (P <.0001). These results show that IFN- can induce a high rate of hematological and cytogenetic response when administered in doses leading to myelosuppression. Factors such as the achievement of CHR and mCR within 3 months could be useful to identify early those patients who will not respond to IFN- and who need alternative treatments such as stem cell transplantation.

Survival after AIDS-defining events in patients with < 200 lymphocytes CD4+ x 10(6)/L who are toxoplasmosis antibody positive. ANRS 005/ACTG 154 Trial Group.

The objective of this study was to assess whether patients with CD4+ cell counts <200 x 10(6)/L have a decreased survival after the occurrence of any AIDS-defining event; 187 patients from the placebo arm of a clinical trial of toxoplasmosis prophylaxis (ANRS005-ACTG154) were included. For this analysis, patients were HIV infected without any AIDS-defining event, had a CD4+ lymphocyte count < 200 x 10(6)/L, had a positive serology for Toxoplasma gondii, and had no severe liver, renal, or hematologic abnormalities. We used proportional hazards regression to study the relationships between baseline variables. AIDS-defining events as time-dependent variables, and survival. The risk of dying was increased by 1.9 for a 10-year increase in age and by 1.3 when CD4+ decreased by 50 x 10(6)/L; after the occurrence of a pneumocystosis, a cytomegalovirus infection, or a toxoplasmosis, the risk of dying was multiplied, respectively, by 10.9 (3.0-40.2), 10.0 (2.8-35.4), and 10.0 (4.5-22.2). None of the other AIDS-defining events was associated with an increased risk of dying, but the power to detect such an association was limited. We conclude that the occurrence of pneumocystosis, cytomegalovirus infection, or toxoplasmosis; age; and CD4+ cell count are important determinants of survival for HIV1-infected patients with CD4+ counts < 200 x 10(6)/L who are toxoplasmosis antibody positive.

Increased risk of toxoplasmic encephalitis in human immunodeficiency virus-infected patients with pyrimethamine-related rash. ANRS 005-ACTG 154 Trial Group. Agence Nationale de Recherche sur le SIDA (ANRS-INSERM) and the NIAID-AIDS Clinical Trials Group.

Although drug-induced rash is frequent in human immunodeficiency virus (HIV)-infected patients, rash due to pyrimethamine has not been described previously. In a randomized, double-blind, placebo-controlled study of pyrimethamine as primary prophylaxis for toxoplasmic encephalitis, the incidence of rash (per hundred patient-years) was 8.1 in the pyrimethamine group versus 1.5 in the placebo group (P < .0002). The 1-year incidence of toxoplasmic encephalitis after occurrence of rash was 37%, as compared with 9.6% in the pyrimethamine group without rash, with a 3.7 times higher risk for patients with pyrimethamine-induced rash (P = .001); the incidence was 13% in the placebo group. At the time of toxoplasmic encephalitis, pyrimethamine was successfully readministered to 80% of patients who discontinued it because of rash. Thus, pyrimethamine, when used for prophylaxis, does induce rash in HIV-infected patients. These patients are at higher risk for toxoplasmic encephalitis and should be carefully monitored for it.

Predictive value of Toxoplasma gondii antibody titres on the occurrence of toxoplasmic encephalitis in HIV-infected patients. ANRS 005/ACTG 154 Trial Group.

OBJECTIVE: To study the predictive value of anti-Toxoplasma gondii antibody titres for the occurrence of toxoplasmic encephalitis (TE) in HIV-infected patients. METHODS: Data from the placebo arm of a trial of primary prophylaxis for TE (ANRS 005/ACTG 154) were analysed. Patients included had CD4+ cell counts < 200 x 10(6)/l and a positive Toxoplasma serology. Immunoglobulin (Ig) G and IgM Toxoplasma antibody titres at entry were retrospectively determined by enzyme-linked immunosorbent assay and agglutination on serum samples in a single laboratory. Incidence of TE was estimated by Kaplan-Meier method and a Cox model was used to study the predictive value of antibody titres, adjusted for other covariates. RESULTS: All 164 patients studied were positive for IgG antibodies and one had IgM antibodies. After a mean follow-up of 16 months, 31 cases of TE were documented. One-year incidence of TE was significantly higher in patients with IgG titres > or = 150 IU/ml (23.7%) than in patients with titres < 150 IU/ml (7.7%; relative risk, 3.1; P < 0.003). IgG titres remained significantly associated with the occurrence of TE (relative risk, 3.3; P < 0.005) in the Cox model. Predictive value of IgG titres did not differ according to baseline CD4+ cell counts. CONCLUSIONS: In patients with CD4+ cell counts < 200 x 10(6)/l, IgG anti-Toxoplasma antibody titre is a prognostic factor of occurrence of TE, with a higher risk for titres > or = 150 IU/ml. This finding should reinforce the recommendation of specific prophylaxis in these patients.

Pyrimethamine for primary prophylaxis of toxoplasmic encephalitis in patients with human immunodeficiency virus infection: a double-blind, randomized trial. ANRS 005-ACTG 154 Group Members. Agence Nationale de Recherche sur le SIDA. AIDS Clinical Trial Group.

Pyrimethamine (50 mg) with folinic acid (15 mg) given three times weekly was assessed as primary prophylaxis for toxoplasmic encephalitis (TE) in 554 human immunodeficiency virus-infected patients seropositive for Toxoplasma gondii and with < 200 CD4 cells/mm3. At 1 year, the incidence of TE was similar in pyrimethamine, 12%, and placebo, 13%, groups (relative risk [RR], 0.9; 95% confidence interval [CI], 0.6-1.4), and the survival rate was also similar, 85% and 80%, respectively (RR, 0.9; 95% CI, 0.7-1.2). Rash was the only adverse event that appeared significantly more frequently in the pyrimethamine arm (7% vs. 1%). In the on-treatment analysis, the incidence of TE was lower in the pyrimethamine arm, 4%, than in the placebo arm, 12% (P < .006). Thus, pyrimethamine cannot be recommended as a first-line regimen for primary prophylaxis of TE if the patient can take cotrimoxazole. However, it should be considered for patients who are intolerant to cotrimoxazole, especially in high-risk patients with < 100 CD4 cells/mm3.

Sindrome de Netherton / Netherton Syndrome

Presentamos dos pacientes con la triada disgnostica del Sindrome de Netherton:ictiosis lineal circunfleja,tricorresis invaginada y diatesis atopica.En ambos casos la biopsia de las lesiones de piel y la microscopia por barrido electronico,fueron decisivas para el diagnostico.Los hallazgos histopatologicos del borde externo de las lesiones fueron compatibles con dermatitis psoriasiforme.La tricorresis invaginada o pelo en caña de bambu,se encontro presente a lo largo del pelo.Las manifestaciones atopicas fueron inconstantes.La edad de los pacientes exigio el planteo de terapeuticas poco agresivas.

Xantogranuloma juvenil / Juvenile xanthogranuloma

Presentamos un paciente de 3 y medio años de edad portador de un xantogranuloma juvenil extendido. Las lesiones fueron atipicas desde el punto de vista clinico e histopatologico y uno de los estudios sugirio el diagnostico de histiocitos x (Granuloma de Celulas de Langerhans).El diagnostico final de Xantogranuloma juvenil se establecio sobre la base del curso benigno de la enfermedad,la normalidad de los hallasgos fisicos y de laboratorio y del estudio de la ultraestructura de la biopsia de piel.

[Risk factors of cerebral toxoplasmosis in patients with HIV infection: data of a primary prevention trial]. / Facteurs de risque de toxoplasmose cérébrale chez les patients infectés par le VIH: données d'un essai de prophylaxie primaire. Groupe d'étude ANRS 005/ACTG 154.

To identify risk factors for cerebral toxoplasmosis (CT) in HIV patients (pts) with positive serology for Toxoplasma gondii and CD4 < 200/mm3, data from the placebo group (N = 280) of a primary prophylaxis trial, were analyzed. The probability of onset of CT (n = 46) was, at one year, 13.1%. Three baseline variables were independently associated with a higher risk of CT: group IV non AIDS, AIDS stage and CD4 < 50/mm3. Initial titer of antibodies to Toxoplasma gondii was not.

Treatment of recurrent common warts with one low dose of intralesional natural human leukocyte interferon alpha.

Nine patients with recurrent and long lasting common warts were treated with intralesional Hu-IFN-alpha. The schedule was a single dose per wart, ranged between 10(5) and 2 x 10(5) IU. Placebo was also administered in 3 of these patients. Complete remission was observed in 7 of the 9 patients. The pattern of warts involution and the possible interferon mechanism of action are discussed. A significant pain relief, produced by interferon injection was observed in the patients with plantar warts and in one patient with subungueal wart.

Epidemiological surveillance of suicides and attempted suicides in Aquitaine, south-west France, using an original computer network of sentinel general practitioners.

To improve the epidemiological study of suicide and attempted suicides in Aquitaine, France, we developed a comprehensive surveillance system based on the input of Sentinel General Practitioners (SGPs). From October 1986 to May 1988, for each case of suicide or attempted suicide, the SGPs reported epidemiological data to our system through a computer network of personal home terminals (Minitels). Data included age, sex, method and result of attempt and antecedents. In an analysis of the relationship between the suicidal method, antecedents and results of suicidal act, the principal findings were a high rate of antecedents of suicide attempts by drug overdoses, hangings and drownings; and no antecedents for attempts by the use of firearms. This may show that the increasing accessibility of firearms is making it more likely that impulsive suicide attempts will be lethal.

Papillomaviruses in human skin warts and their incidence in an Argentine population.

Human papillomavirus genomic types present in human warts of an Argentine population were studied. HPV DNA from single warts was obtained using an alkaline extraction procedure that resulted in a clean DNA preparation, which could be analyzed with several endonucleases. This method was used to isolate and insert the HPV DNAs of two genomic types into the Bam HI site of the pBR322 plasmid. Restriction maps of both HPV DNAs were constructed. According to these maps, one of the genomic variations was identical to HPV1a and the other to HPV2a. The incidence of HPV2 and of HPV1 in different types of skin warts was studied by a dot blot hybridization assay. Twenty-two out of 28 common warts were positive for HPV2 and negative for HPV1; four were positive for HPV1 and negative for HPV2 and two were negative for both. Five out of six plantar warts were positive for HPV1, and one was negative for both. Three out of seven filiform warts were positive for HPV2, three were positive for both probes, and one was negative for both. Southern blot analysis of HPV2 positive samples indicated that 80% were HPV2a and 20% another subtype not yet characterized. All plantar warts contained HPV1a. Msp I/Hpa II restriction analysis confirms previous results indicating that HPV1a DNA is partially methylated, while no evidence of methylation was found for HPV2a DNA.

[Therapeutic use of human leukocyte interferon in dermatologic disorders caused by herpes simplex virus. Multicenter study]. / Uso terapéutico de interferón leucocitario humano en lesiones dermatológicas producidas por el virus del herpes simple. Estudio multicéntrico.

A multi-institutional double blind study was performed in 66 patients in order to evaluate the action of human leukocyte interferon, type alpha (IFN) in lesions produced by herpes simplex virus. Lesions were localized in genital area in 34 cases and in facial area in 32 of them. From the total, 38 patients were treated with 7,000 Ul/gm. of interferon ointment and 28 with carbowax 4,000 as placebo. The symptoms pain, ardor, itching and paresthesia were evaluated asking to patients. Erythema, vesicles, crust, scale adenopathy were objectivated. Signs and symptoms were controlled on days 3 and 7 of treatment. In 42 patients, lesions specimens were taken for virus isolation. In 23 of them, cytopathic effect was detected (54.76%). Results showed a rapid relief from pain (p less than 0.05), ardor (p less than 0.01) and paresthesia (p less than 0.001) and also accelerated healing of vesicles in patients treated with interferon. Tendency to reduce the total time of the disease in those patients treated with IFN was observed.

Dermatosis ampollar crónica benigna del niño / Benign chronic bullous dermatosis of children

Presentamos a una niña de 3 y medio años de edad que padece una dermatosis ampollar crónica benigna del niño. El diagnóstico se basa sobre criterios clínicos, anatomopatológicos, inmunológicos, terapéuticos y de microscopía electrónica. En tres estudios de inmunofluorescencia directa y en uno de inmunofluorescencia indirecta no se demonstraron anticuerpos epiteliales fijos ni circulantes. Consideramos a este como el verdadero patrón inmunológico de la DACBN ya que el hallazgo de IgA lineal en otros pacientes los hace homologables a la dermatosis ampollar IgA lineal del adulto. El estudio de antígenos de histocompatibilidad reveló un HLA B 8. Se comenta la evolución y tratamiento en 15 meses de seguimiento

Queratodermia con periodontosis (Papillon-Lefevre). / Keratoderma with periodontosis (Papillon-Lefevre)

Se comunica un caso de sindrome de Papillon-Lefevre en una nina de 11 anos.A pesar de que presentaba queratodermia desde los 9 meses de edad y caida de piezas dentarias con flemones bucales recidivantes, el diagnostico fue hecho en el Servicio de Toxicologia