Dabrafenib plus trametinib in patients with BRAF V600E-mutant anaplastic thyroid cancer: updated analysis from the phase II ROAR basket study.

BACKGROUND: Combined therapy with dabrafenib plus trametinib was approved in several countries for treatment of BRAF V600E-mutant anaplastic thyroid cancer (ATC) based on an earlier interim analysis of 23 response-assessable patients in the ATC cohort of the phase II Rare Oncology Agnostic Research (ROAR) basket study. We report an updated analysis describing the efficacy and safety of dabrafenib plus trametinib in the full ROAR ATC cohort of 36 patients with ∼4 years of additional study follow-up. PATIENTS AND METHODS: ROAR (NCT02034110) is an open-label, nonrandomized, phase II basket study evaluating dabrafenib plus trametinib in BRAF V600E-mutant rare cancers. The ATC cohort comprised 36 patients with unresectable or metastatic ATC who received dabrafenib 150 mg twice daily plus trametinib 2 mg once daily orally until disease progression, unacceptable toxicity, or death. The primary endpoint was investigator-assessed overall response rate (ORR) per Response Evaluation Criteria in Solid Tumors version 1.1. Secondary endpoints were duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety. RESULTS: At data cutoff (14 September 2020), median follow-up was 11.1 months (range, 0.9-76.6 months). The investigator-assessed ORR was 56% (95% confidence interval, 38.1% to 72.1%), including three complete responses; the 12-month DOR rate was 50%. Median PFS and OS were 6.7 and 14.5 months, respectively. The respective 12-month PFS and OS rates were 43.2% and 51.7%, and the 24-month OS rate was 31.5%. No new safety signals were identified with additional follow-up, and adverse events were consistent with the established tolerability of dabrafenib plus trametinib. CONCLUSIONS: These updated results confirm the substantial clinical benefit and manageable toxicity of dabrafenib plus trametinib in BRAF V600E-mutant ATC. Dabrafenib plus trametinib notably improved long-term survival and represents a meaningful treatment option for this rare, aggressive cancer.

Revealing time's secrets at the National Theatre of Costa Rica via innovative software for cultural heritage research.

Establishing affordable, efficient, accessible, innovative, and multidisciplinary methodologies to the diagnosis of the conservation state of an artwork is key to carry out appropriate strategies of conservation and consequently to the creation of modern public policies on cultural heritage. Limited access to large-format paintings is a challenge to restoration scientists seeking to obtain information quickly, in a non-destructive and non-invasive manner, and identify regions of interest. Therefore, we put forward two unique software tools based on multispectral imaging techniques, with the long-term aim to assess the artist's intentions, creative process, and colour palette. This development paves the way for a comprehensive and multidisciplinary understanding of the mysteries encompassed in each pictorial layer, through the study of their physical and chemical characteristics. We conducted the first ever study on Musas I and Musas II, two large-format paintings by Italian artist Carlo Ferrario, located in the National Theatre of Costa Rica. In this study, we used our novel imaging techniques to choose regions of interest in order to study sample layers; while also assessing the works' state of conservation and possible biodeterioration. We explored the applications of our two versatile software tools, RegionOfInterest and CrystalDistribution, and confirmed paint stratigraphies by means of microscopy and spectroscopy analyses (OM, SEM-EDX, Fluorescent microscopy, FTIR-ATR and micro-Raman). In a pilot study, we identified the artist's main colour palette: zinc white, lead white, chrome yellow, lead read, viridian, along with artificial vermilion and ultramarine pigments. We were able to identify artificial vermilion and ultramarine and distinguish them from the natural pigments using CrystalDistribution to map the average size and diameter of the pigment crystals within the paint layers. This study demonstrated that software-based multidisciplinary imaging techniques are novel in establishing preventive and non-invasive methods for historical painting conservation studies, in addition, this study provides tools with great potential to be used in the future in applications such as virtual restoration.

Prostatectomía radical robot-asistida con preservación del espacio de Retzius: resultados perioperatorios y de continencia inmediata en una serie inicial / Retzius-sparing robot-assisted radical prostatectomy: Perioperative and immediate continence outcomes of an initial series

OBJETIVO: Los objetivos de este trabajo son presentar los resultados perioperatorios, de continencia inmediata y oncológicos iniciales en una serie de 25 pacientes con cáncer de próstata tratados con prostatectomía radical robot-asistida con preservación del espacio de Retzius. MATERIAL Y MÉTODOS: Analizamos retrospectivamente una serie de 25 pacientes tratados con prostatectomía radical robótica con preservación del espacio de Retzius por cáncer de próstata cT1-T2b entre 2018-2019. Se describen las 5 etapas de la cirugía. Efectuamos una estadística descriptiva de nuestra serie inicial y sus resultados en términos de continencia inmediata, definida como el uso de 0 compresas/pañales o 1 por seguridad/24 horas en la primera semana tras retirada de la sonda. RESULTADOS: Mediana de seguimiento, 6 meses (3-18). Mediana de PSA, 6,1 ng/ml (4-14,3). Todas las cirugías se realizan por vía posterior e intrafascial con preservación neurovascular bilateral en el 84% de los casos. El 28% tienen un margen quirúrgico afectado siendo el ápex la zona de afectación más frecuente. Complicaciones quirúrgicas: 1 (4%) paciente requirió transfusión de hemoderivados en el postoperatorio inmediato. Mediana de estancia hospitalaria 48 horas. Resultados funcionales: el 80% tiene continencia inmediata. El 80% de los continentes no requiere el uso de ningún pañal/compresa de seguridad. Resultados oncológicos: el 84% están libres de progresión bioquímica con una mediana de seguimiento de 6 meses. CONCLUSIONES: Los resultados funcionales iniciales en términos de continencia inmediata son muy satisfactorios en pacientes intervenidos de prostatectomía radical robótica con preservación del espacio de Retzius sin impacto negativo en el pronóstico

OBJECTIVE: The objective of this work is to present initial perioperative, immediate continence and oncological results in a series of 25 prostate cancer patients treated with Retzius-sparing robot-assisted radical prostatectomy. MATERIAL AND METHODS: We retrospectively analyzed a series of 25 patients treated with Retzius-sparing robot-assisted radical prostatectomy for cT1-T2b prostate cancer between 2018-2019. The 5 stages of surgery are described. We make a descriptive statistic of our initial series and its outcomes in terms of immediate continence, defined as the use of 0 pad/diapers or 1 safety pad/diaper every 24 hours, one week after catheter removal. RESULTS: Median follow-up, 6 months (3-18). Median PSA, 6.1 ng/ml (4-14.3). All surgeries were performed through a posterior intrafascial approach, and bilateral nerve-sparing was carried out in 84% of the cases. Affected surgical margins were present in 28%, being the apex the most frequent site of affectation. Surgical complications: 1 (4%) patient required transfusion of blood products in the immediate postoperative period. Mean hospital stay was 48 hours. Functional outcomes: 80% of the patients present immediate continence. 80% of continent patients do not require the use of any safety pads/diapers. Oncological outcomes: 84% are free of biochemical-progression in a median follow-up of 6 months. CONCLUSIONS: Initial functional results in terms of immediate continence are very satisfactory in patients who have undergone Retzius-sparing robot-assisted radical prostatectomy without negative impact on prognosis

Retzius-sparing robot-assisted radical prostatectomy: Perioperative and immediate continence outcomes of an initial series. / Prostatectomía radical robot-asistida con preservación del espacio de Retzius: resultados perioperatorios y de continencia inmediata en una serie inicial.

OBJECTIVE: The objective of this work is to present initial perioperative, immediate continence and oncological results in a series of 25 prostate cancer patients treated with Retzius-sparing robot-assisted radical prostatectomy. MATERIAL AND METHODS: We retrospectively analyzed a series of 25 patients treated with Retzius-sparing robot-assisted radical prostatectomy for cT1-T2b prostate cancer between 2018-2019. The 5 stages of surgery are described. We make a descriptive statistic of our initial series and its outcomes in terms of immediate continence, defined as the use of 0 pad/diapers or 1 safety pad/diaper every 24 hours, one week after catheter removal. RESULTS: Median follow-up, 6 months (3-18). Median PSA, 6.1 ng/ml (4-14.3). All surgeries were performed through a posterior intrafascial approach, and bilateral nerve-sparing was carried out in 84% of the cases. Affected surgical margins were present in 28%, being the apex the most frequent site of affectation. Surgical complications: 1 (4%) patient required transfusion of blood products in the immediate postoperative period. Mean hospital stay was 48 hours. Functional outcomes: 80% of the patients present immediate continence. 80% of continent patients do not require the use of any safety pads/diapers. Oncological outcomes: 84% are free of biochemical-progression in a median follow-up of 6 months. CONCLUSIONS: Initial functional results in terms of immediate continence are very satisfactory in patients who have undergone Retzius-sparing robot-assisted radical prostatectomy without negative impact on prognosis.

Intervención grupal del síndrome subacromial en atención primaria / A group intervention for shoulder impingement syndrome in primary care

Introducción. El aumento de consultas por dolor de hombro en los servicios de rehabilitación impone buscar alternativas eficientes para mejorar su manejo. Objetivos. Evaluar la efectividad de un programa de rehabilitación grupal para mejorar la funcionalidad y el dolor en pacientes afectos de síndrome subacromial y ver qué variables se asocian a un mejor resultado funcional final. Métodos. Estudio longitudinal prospectivo de intervención antes/después. Muestra: 211 pacientes. La intervención consistió en 10 sesiones de electroterapia analgésica individual, 5 sesiones de cinesiterapia grupal y una sesión informativa: «escuela de hombro». El seguimiento fue de un año. Medimos la funcionalidad con el test de Constant y el dolor con la escala visual analógica. Pruebas estadísticas: chi cuadrado, T-test, ANOVA y regresión lineal múltiple (p < 0,05). Resultados. La funcionalidad mejoró significativamente en los 4 períodos estudiados respecto al valor inicial y se estabilizó a los 6 meses. El perfil de paciente que obtuvo mayor funcionalidad fue: mujer, mayor de 60 años, sin dolor en reposo inicial y laboralmente no activa. La mejora del dolor observada a largo plazo no fue significativa. El consumo de analgésicos se redujo significativamente a los 3 meses. La adherencia al tratamiento domiciliario de ejercicios fue del 81% a los 3 y 6 meses y del 70,6% al año. Conclusiones. La aplicación de un programa de rehabilitación grupal en pacientes afectos de síndrome subacromial se ha mostrado efectivo para mejorar la funcionalidad a largo plazo. Sin embargo, el dolor no ha mostrado mejoría significativa a lo largo del estudio (AU)

Introduction. Due to the increase in consultations for shoulder pain in rehabilitation services, there is a need for efficient alternatives to improve the management of this disorder. Objectives. To evaluate the effectiveness of a supervised group exercise program to improve functionality and pain in patients with shoulder impingement syndrome and to identify the variables that are associated with a better functional outcome. Methods. A prospective longitudinal, pre and post intervention study was carried out in a sample of 211 patients. The treatment consisted of 10 individual sessions of analgesic electrotherapy, 5 sessions of group exercise therapy and an educational session: «shoulder school». One year follow-up was performed. Shoulder function and pain were assessed using Constant's test and the visual analogue scale. The statistical analysis was carried out with the chi-square test, T-test, ANOVA and multiple linear regression (P < .05). Results. Functionality improved significantly in all periods studied compared with baseline and stabilized at 6 months. The profile of patients who achieved greater functionality was female, older than 60 years, with no initial rest pain and occupationally inactive. Long-term pain improvement was not significant. Analgesic use was significantly reduced at 3 months. Adherence to home exercise treatment was 81% at 3 and 6 months and 70.6% at one year. Conclusions. The application of a group rehabilitation program in patients with shoulder impingement syndrome was effective in improving long-term functionality. However, there was no significant pain improvement during the study (AU)

Hialohifomicosis invasiva hepatoesplénica: comunicación de un caso / Hepatosplenic hialohifomycosis: report of 1 case

Invasive fungal infections are an increasingly common problem in patients with cancer and other vulnerable groups. We report a case of hepatosplenic hialohifomycosis probably by Aspergillus sp. In a patient with acute leukemia, and prolonged neutropenia, treated with corticosteroids and broad spectrum antibiotics. A review concerning diagnosis, clinical course and treatment of this condition is presented

Gender differences in children's hospitalization in Catalonia: another inequality?

The aim of this study was to describe children's hospitalization and to analyse gender differences by selected diagnostic and procedure groups. Using the Clinical Classification for Health Policy Research Version 2 (CCHPR), 81 888 hospitalizations from the Minimum Basic Data Set of Hospital Discharge (CMBDAH) of 1995 related to children under 15 y of age in Catalonia, Spain, were studied. Hospitalization rates, number of days in hospital, average length of stay (d) in hospital and the standardized hospitalization ratio (SHR) (hospitalization rate in boys/hospitalization rate in girls) were computed. Two independent approaches were taken: (i) gender-specific categories were excluded in order to compare hospitalizations by sex; (ii) a selected group of 17 diagnostic and procedure categories were chosen in order to carry out the specific gender comparison. In both approaches, the selected indicators were compared by age groups, and totals were standardized by age using the direct method. An excess of hospitalization in boys was observed (SHR = 1.18; 95% CI: 1.17-1.19). The number of days spent in hospital and hospitalization rates were higher in infants and were also higher for boys than for girls. The average length of stay in hospital was higher in infants and in girls at all ages. These differences were systematic when stratified by health region, admission and discharge circumstances and hospital category. Except for urinary infection, which was higher in girls (SHR: 0.65; CI 95%: 0.54-0.76), the SHR was higher in boys in all diagnostic and procedure categories analysed (all SHR >1). Specific sex categories, injuries and poisonings cannot on their own explain a higher level of hospitalization among boys. More specific studies are needed to explain the role of the family and the healthcare system in gender inequalities in children's hospitalization.

Nitric oxide-mediated apoptosis of K-1735 melanoma cells is associated with downregulation of Bcl-2.

Recent studies have shown that the treatment of nonmetastatic K-1735 murine melanoma cells with cytokines induces the production of nitric oxide (NO) and hence cell death. The purpose of this study was to determine the mechanism of this cytokine-induced NO-mediated apoptosis. Incubation of nonmetastatic K-1735 cells with interleukin-1 alpha (IL-1alpha) and interferon-gamma (IFN-gamma) induced high NO production, Bcl-2 downregulation, and apoptotic cell death. In contrast, incubation of metastatic K-1735 cells with IL-1alpha and IFN-gamma did not induce significant production of NO, downregulation of Bcl-2, or cell death. The exposure to exogenous NO derived from the NO donors, sodium nitroprusside (SNP), or GEA5024 produced a dose-dependent apoptotic cell death in both the metastatic and nonmetastatic K-1735 cells, which was associated with downregulation of Bcl-2 at the mRNA level and, to a lesser extent, at the protein level. Nonmetastatic and metastatic K-1735 cells transfected with the Bcl-2 gene were more resistant to apoptosis mediated by both endogenous and exogenous NO. Subsequent to intravenous injection, the tumor cells transfected with the Bcl-2 gene had an increased survival rate in the lungs of nude mice and produced a higher number of experimental lung metastases. These data suggest that NO-induced apoptosis in K-1735 melanoma cells is associated with downregulation of Bcl-2.

Abrogation of tumorigenicity and metastasis of murine and human tumor cells by transfection with the murine IFN-beta gene: possible role of nitric oxide.

The purpose of this study was to determine whether sustained local production of murine IFN-beta (mIFN-beta) could inhibit the tumorigenicity and metastasis of human and murine tumor cells implanted into nude mice. Human melanoma cells (A375SM), renal carcinoma cells (SN12PM6), and colon carcinoma cells (KM12SM) were transfected with mIFN-beta or a control neomycin resistance vector. All cell lines grew well in culture. Tumor cells were injected into the subcutis, kidney, spleen, or lateral tail vein of nude mice. Parental or control transfected cells produced local tumors and experimental or spontaneous lung metastases, whereas mIFN-beta-transfected cells did not. In vivo survival experiments using [125I]IdUdR-labeled cells showed that by day 7 after s.c. implantation, all IFN-beta-transfected cells died. IFN-beta transfection prevented the outgrowth of parental or control-transfected cells only when they were injected together with transfected cells into one site, suggesting that IFN-beta promoted a local lysis of the bystander cells. Similar indirect antitumor activity was demonstrated in various human (KM12SM and SN12PM6) and murine (CT-26 colon carcinoma, RENCA renal cell carcinoma, and 3LL Lewis lung carcinoma) tumors. The IFN-beta-transfected tumor cells stimulated a high level of nitric oxide production by murine macrophages under in vitro and in vivo conditions, which correlated with the vigorous nonspecific antitumor activity. Collectively, these results demonstrate that local production of IFN-beta can eradicate tumor cells of different histology by inducing inducible nitric oxide synthase expression in infiltrating cells.

A Tat-induced auto-up-regulatory loop for superactivation of the human immunodeficiency virus type 1 promoter.

The virus-encoded Tat protein strongly activates transcription of human immunodeficiency virus (HIV). A well-recognized mechanism involves interaction of Tat with the nascent RNA transcript of the viral tar gene; mutation of tar greatly decreases activation by Tat. However, Tat still provides a low level of activation, demonstrating that it also has a tar-independent mode of action. We propose that this tar-independent mode of Tat action is through activation of gene transcription to produce tumor necrosis factor alpha. This cytokine and other compounds that activate NF-kappa B up-regulate the HIV promoter at a low level, similarly to the second Tat action. Through this mechanism, they also activate promoters of tumor necrosis factor alpha and other cytokines and thereby establish an auto-up-regulatory loop. Activated NF-kappa B motifs in the HIV promoter synergize with Tat/tar. Mutations of these motifs decrease activation by Tat to a few percent of the wild-type value. In cooperation, the two modes of activation by Tat (tar dependent and cytokine based) set up positive up-regulatory loops which greatly superactivate transcription of HIV. Agents that block these synergistic pathways at three different steps and are more inhibitory in combination than is any one alone have been found. Thereby, multidrug modalities for transcription of HIV are proposed for virus suppression.

Potential applications of proviral load measurement in clinical retrovirology.

We have previously noted an association between proviral load and the severity of immune disease in individuals with a wide range of CD4 cell counts. Using the quantitative DNA polymerase chain reaction technology developed in our laboratory, we sought to extend these observations, with a view to establishing guidelines for the use of proviral load in a clinical context. We studied 199 patients with a range of CD4 cell counts attending an urban tertiary care center. Proviral load/10(6) peripheral blood mononuclear cells (PBMCs) was measured using a microtiter plate assay designed specifically for this purpose. Human immunodeficiency virus proviral DNA was detected in 193 of 199 clinical samples. Levels of proviral load were tabulated for patients and evaluated in seven categories defined by CD4 cell counts. Although a wide range of proviral loads was observed in each category of patients, there was a trend toward increasing proviral load with decreasing CD4 cell count. Statistically significant relationships were observed between proviral load and the CD4 cell count and the CD4 cell percentage (Spearman's correlation coefficient -0.19, p = 0.01 for both absolute CD4 and CD4 percentage). These relationships were quite weak and could not be taken to explain disease progression in isolation. If we defined a cutoff between low and high proviral loads at 100 copies/10(6) PBMCs, we noted that 52% (24 of 46) of patients with CD4 cell counts > 400/microliters had lower loads, as compared with 16% (24 of 143) of those with more advanced disease (p < 0.01). There is a weak, but statistically significant association between proviral load and CD4 cell depletion.(ABSTRACT TRUNCATED AT 250 WORDS)

[An improvement in the AIDS mortality statistics in Catalonia]. / Mejora de las estadísticas de mortalidad por SIDA en Cataluña.

Differences between the number of AIDS death reported to the mortality register and to the AIDS register in Catalonia, Spain are relatively small, due to bot registers cooperation. Official mortality statistics are able to identify 78% of AIDS deaths. This proportion can be increased if the deaths caused by AIDS indicative diseases are included. The overall proportion of false positives when comparing both registers is 8.2%. Analysis of the available information from death certificates is useful to suggest simple recommendation to improve the quality of AIDS mortality data.

Ascaris en vias biliares: casos clínicos / Ascariasis in biliary channels: clinical cases

La ascaris es una enfermedad parasitaria por Ascaris Lumbricoides. Se caracteriza por ser un gusano redondo, grande, nematodo intestinal blanquecino; la hembra es de mayor dimensión que el macho; particularmente abunda en los trópicos y lugares con malas condiciones de salubridad. Uno de cada 4 habitantes en el mundo está infectado por áscaris. Este reporte describe a una paciente de 25 años y otra de 58 años, que presentaron similar evolución clínica. Es importante saber diagnosticar, puesto que la clínica depende del número de vermes y su localización; en la infestación leve es posible el curso asintomático o solo ligeros síntomas abdominales. Las cargas mayores inclusive ocasionan obstrucción intestinal, puede migrar y llegar al exterior por la boca o la nariz, otras veces obstruye el conducto biliar (25xciento), páncreas o apéndice (5). Se diagnostica mediante la identificación de huevos de áscaris en las heces, eosinofilia, colangiografía intravenosa, ecosonografía, observándose claramente áscaris en vías biliares...

Trends and survival in AIDS-associated malignancies.

Data from 1569 AIDS cases reported to the population-based AIDS Registry of Catalonia have been analysed to describe the epidemiology and temporal evolution of both Kaposi's sarcoma (KS) and non-Hodgkin lymphoma (NHL). Of the 1569 cases reported, 53 (3.4%) presented with NHL and 135 (8.6%) with KS. KS cases were more frequent among homosexual/bisexual men and the age of KS cases was significantly higher than all others presenting diseases (38.22 years). NHL cases were more frequently among men but no significant age difference was found. The percentage of KS over time decreased significantly only among intravenous drug users. Cases presenting with a NHL had by far the worst prognosis (median survival time = 169 days). Biases affecting the measurement of AIDS associated malignancies (AAM) using surveillance data are analysed. The prevalence of AAM will increase during the next few years, and NHL may be one of the leading causes of death among AIDS patients in the near future.

Stability of dried blood spot specimens for detection of human immunodeficiency virus DNA by polymerase chain reaction.

Blood sampling on filter paper has many advantages for the detection of perinatal human immunodeficiency virus (HIV) infection by the polymerase chain reaction (PCR). However, if the method is to be widely used, an assessment of its performance under field conditions is required. To simulate conditions in the field, 50-microliters aliquots of whole blood containing low levels of HIV proviral DNA (4 to 1,024 copies per 100,000 nucleated cells) were spotted onto filter paper; dried; and subjected to heat, humidity, and prolonged storage at room temperature. After exposure, the DNA was recovered and amplified with primers to human leukocyte antigen DQ alpha- and HIV-specific sequences. Treatment at 37 degrees C and 60% humidity for 7 days, storage for 12 weeks at 22 degrees C, and freeze-thawing twice had no adverse effect on PCR reactivity when compared with the results obtained with reference spots stored at -20 degrees C. The lower limits of HIV detection in all tests ranged from 4 to 16 HIV copies per 100,000 cells. Fixation in 70% ethanol improved the amplification of low levels of HIV DNA and reduced biohazard risks. These findings suggest that dried blood spots will provide a powerful new resource for testing for HIV by PCR, especially in remote areas where refrigeration and immediate sample processing are unavailable.

Rapid DNA fingerprinting to control for specimen errors in HIV testing by the polymerase chain reaction.

Variable-number-tandem-repeats (VNTRs) are highly polymorphic and provide informative genetic markers for distinguishing between individuals. We have used PCR amplification of VNTR locus pMCT118 to identify mislabelled specimens submitted for HIV PCR testing. The method is rapid, can be applied to large numbers of samples and eliminates the need for radioactive probes. DNA samples (10 ng) are amplified for 25 cycles using fluorescence-labelled oligonucleotide primers (blue dye). An aliquot of the PCR product is then combined with an internal lane size standard (labelled with a red dye), electrophoresed through a 2% agarose gel on an automated fluorescence DNA fragment analyser and the size and quantity of the fragments determined automatically relative to the internal standard. Fifteen alleles, ranging in size from 398 tp 709 bp were readily identified in a random sampling of DNA from 63 unrelated HIV-infected patients. Fragment size was reproducible and corresponded to alleles containing from 16 to 35 repeats of a 16 bp unit. VNTR genotyping will prove useful for resolving discordant results due to specimen mix-up and ensuring that the correct samples have been analyzed.

OLIGSCAN: a computer program to assist in the design of PCR primers homologous to multiple DNA sequences.

OLIGSCAN (oligonucleotide scanner) is a computer program for IBM-PC-compatible computers that allows the user to scan up to 200 DNA sequences for homology to oligonucleotide sequences of interest. Once a core sequence of longer than the user-defined minimum length is found, the remainder of the oligonucleotide is compared to the corresponding positions of the larger sequence to identify matches or mismatches flanking the core region. This algorithm results in identification of the longest possible homologous regions first. The program was originally designed to assist in the identification of potential annealing sites for polymerase chain reaction (PCR) primers in the genomic DNA of related strains of viruses. However, it may also be used for more general pattern-identification purposes, including scanning for various sequence motifs of functional importance. We present the analysis of homology to an oligonucleotide primer in 16 complete genomic sequences of the human and simian immunodeficiency viruses.

Detection of incident HIV infection by PCR compared to serology.

In order to determine the most sensitive method for the early detection of HIV infection, polymerase chain reaction (PCR) and serology were compared using matched peripheral blood mononuclear cells (PBMC) and serum samples taken sequentially at 3-month intervals on 17 HIV seroconverters. All samples from the time of enrollment in the study to the time of seroconversion were studied. [There were only two of the 17 cases where PCR and antigen positivity preceded EIA detectable seroconversion.] Initially, one of these cases was found to be PCR positive 11 months prior to seroconversion, however DNA fingerprinting techniques indicated that the early positive specimen did not belong to the subject in question. In a single subject, PCR was negative at the time of serologic evidence of infection but was positive at the next sampling 3 months later. In the remaining 14 cases, PCR was positive at the same sample time as full or partial seroconversion as determined by three EIA screening tests and Western blot. EIA antibody screen tests showed variability in detection of early HIV antibodies. We found no evidence for prolonged HIV infection prior to seroconversion. PCR offers little if any advantage over serology in the early detection of HIV infection in adults.