Clinical characteristics and evolution of syphilis in 24 HIV+ individuals in Rio de Janeiro, Brazil

A total of 24 patients with syphilis and HIV infection were treated from January 1997 to March 2003 at the Infectious Dermatology Outpatient Clinic of the Evandro Chagas Clinical Research Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil. The caseload consisted of 20 males (83.3%) and four females (16.7%), with a mean age of 38.04 years and mean T CD4+ count of 389.5 cells/mL. Syphilis was diagnosed as secondary in 16 (62.5%) patients, late latent in eight (33.3%), and tertiary in one (4.2%). Manifestations of secondary syphilis were palmar and plantar erythematopapulous cutaneous lesions in nine (37.5%), papulous exanthema in four (16.7%), patchy alopecia in 3 (12.5%) and osteochondritis in one patient (4.2%). Tertiary syphilis was characterized by verrucous lesions. Neurosyphilis was diagnosed in four patients (16.7%), with headache as the only manifestation in two patients. Drugs used in treatment included benzathine penicillin, ceftriaxone, erythromycin, and crystalline penicillin. Cure was achieved in 18 patients (75%). Five patients (20.8%) were retreated, three of whom presented a history of re-exposure. This study confirms the importance of establishing the diagnosis of neurosyphilis in patients with HIV infection, in addition to performing follow-up on treatment for syphilis.

Abdominal angiostrongyliasis: a case with severe evolution

A case of acute abdomen disease caused by abdominal angiostrongyliasis is reported. A 42-year-old otherwise healthy patient presented with a complaint of nine days of abdominal pain, constipation, disury, fever and right iliac fossa palpable mass. Exploratory laparotomy was performed. After surgical treatment the patient presented serious complications.

Indications of carbapenem resistance evolution through heteroresistance as an intermediate stage in Acinetobacter baumannii after carbapenem administration

We describe an in vivo evolution of an antimicrobial profile from susceptibility to full-resistance to carbapenems, with heteroresistance as an intermediate stage, in an Acinetobacter baumannii strain. Heteroresistance was characterized by the growth of sub-populations within the susceptibility halo in both disk-diffusion and Etest. PCRs for the main A. baumannii carbapenemases were negative. The exact resistance mechanism, diagnostic methods and clinical relevance of heteroresistance in A. baumannii warrant further investigations. This is the first description of such phenomenon in vivo and the second report of heteroresistance to carbapenems in A. baumannii.

EVOLUTION OF PATIENTS WITH AIDS AFTER cART: CLINICAL AND LABORATORY EVOLUTION OF PATIENTS WITH AIDS AFTER 48 WEEKS OF ANTIRETROVIRAL TREATMENT

SUMMARY Combination Antiretroviral Therapy (cART) aims to inhibit viral replication, delay immunodeficiency progression and improve survival in AIDS patients. The objective of this study was to compare two different schemes of cART, based on plasma viral load (VL) and CD4+ T lymphocyte count, during 48 weeks of treatment. For this purpose, 472 medical charts of a Specialized Outpatient Service were reviewed from 1998 to 2005. Out of these, 58 AIDS patients who had received a triple drug scheme as the initial treatment were included in the study and two groups were formed: Group 1 (G1): 47 individuals treated with two nucleoside reverse-transcriptase inhibitors (NRTI) and one non-nucleoside reverse-transcriptase inhibitor; Group 2 (G2): 11 patients treated with two NRTI and one protease inhibitor. In G1 and G2, 53.2% and 81.8% respectively were patients with an AIDS-defining disease. The T CD4+ lymphocyte count increased progressively up until the 24th week of treatment in all patients, while VL became undetectable in 68.1% of G1 and in 63.6% of G2. The study concluded that the evolutions of laboratory tests were similar in the two treatment groups and that both presented a favorable clinical evolution.

BODY WEIGHT AS A DETERMINANT OF CLINICAL EVOLUTION IN HAMSTERS (Mesocricetus auratus) INFECTED WITH Leishmania (Viannia) panamensis

SUMMARY The clinical outcome of infection with Leishmania species of the subgenus Viannia in hamster model (Mesocricetus auratus) has shown to be different depending on experimental protocol. Body weight has been a relevant determinant of the clinical outcome of the infection in hamsters with visceral leishmaniasis but its importance as a clinical parameter in hamsters with cutaneous leishmaniasis is not known. In this study, the clinical evolution of infection with L. (V) panamensis was evaluated in juvenile and adult male hamsters during 11 weeks by comparing clinical parameters such as attitude, temperature, respiratory rate, appearance of the stool, and body weight between infected and non-infected groups. Results showed that body weight decreased in adult hamsters after infection by L. (V) panamensis; this observation supports the use of body weight as an additional parameter to define the management or treatment of cutaneous leishmaniasis in infected adult hamsters used as an animal experimental model for leishmaniasis.

The Role of the Humoral Immune Response in the Molecular Evolution of the Envelope C2, V3 and C3 Regions in Chronically HIV-2 Infected Patients

BACKGROUND: This study was designed to investigate, for the first time, the short-term molecular evolution of the HIV-2 C2, V3 and C3 envelope regions and its association with the immune response. Clonal sequences of the env C2V3C3 region were obtained from a cohort of eighteen HIV-2 chronically infected patients followed prospectively during 2-4 years. Genetic diversity, divergence, positive selection and glycosylation in the C2V3C3 region were analysed as a function of the number of CD4+ T cells and the anti-C2V3C3 IgG and IgA antibody reactivity RESULTS: The mean intra-host nucleotide diversity was 2.1% (SD, 1.1%), increasing along the course of infection in most patients. Diversity at the amino acid level was significantly lower for the V3 region and higher for the C2 region. The average divergence rate was 0.014 substitutions/site/year, which is similar to that reported in chronic HIV-1 infection. The number and position of positively selected sites was highly variable, except for codons 267 and 270 in C2 that were under strong and persistent positive selection in most patients. N-glycosylation sites located in C2 and V3 were conserved in all patients along the course of infection. Intra-host variation of C2V3C3-specific IgG response over time was inversely associated with the variation in nucleotide and amino acid diversity of the C2V3C3 region. Variation of the C2V3C3-specific IgA response was inversely associated with variation in the number of N-glycosylation sites. CONCLUSION: The evolutionary dynamics of HIV-2 envelope during chronic aviremic infection is similar to HIV-1 implying that the virus should be actively replicating in cellular compartments. Convergent evolution of N-glycosylation in C2 and V3, and the limited diversification of V3, indicates that there are important functional constraints to the potential diversity of the HIV-2 envelope. C2V3C3-specific IgG antibodies are effective at reducing viral population size limiting the number of virus escape mutants. The C3 region seems to be a target for IgA antibodies and increasing N-linked glycosylation may prevent HIV-2 envelope recognition by these antibodies. Our results provide new insights into the biology of HIV-2 and its relation with the human host and may have important implications for vaccine design.

Evolution of the Human Immunodeficiency Virus Type 2 Envelope in the First Years of Infection is Associated with the Dynamics of the Neutralizing Antibody Response

Background: Differently from HIV-1, HIV-2 disease progression usually takes decades without antiretroviral therapy and the majority of HIV-2 infected individuals survive as elite controllers with normal CD4+ T cell counts and low or undetectable plasma viral load. Neutralizing antibodies (Nabs) are thought to play a central role in HIV-2 evolution and pathogenesis. However, the dynamic of the Nab response and resulting HIV-2 escape during acute infection and their impact in HIV-2 evolution and disease progression remain largely unknown. Our objective was to characterize the Nab response and the molecular and phenotypic evolution of HIV-2 in association with Nab escape in the first years of infection in two children infected at birth. Results: CD4+ T cells decreased from about 50% to below 30% in both children in the first five years of infection and the infecting R5 viruses were replaced by X4 viruses within the same period. With antiretroviral therapy, viral load in child 1 decreased to undetectable levels and CD4+ T cells recovered to normal levels, which have been sustained at least until the age of 12. In contrast, viral load increased in child 2 and she progressed to AIDS and death at age 9. Beginning in the first year of life, child 1 raised high titers of antibodies that neutralized primary R5 isolates more effectively than X4 isolates, both autologous and heterologous. Child 2 raised a weak X4-specific Nab response that decreased sharply as disease progressed. Rate of evolution, nucleotide and amino acid diversity, and positive selection, were significantly higher in the envelope of child 1 compared to child 2. Rates of R5-to-X4 tropism switch, of V1 and V3 sequence diversification, and of convergence of V3 to a β-hairpin structure were related with rate of escape from the neutralizing antibodies. Conclusion: Our data suggests that the molecular and phenotypic evolution of the human immunodeficiency virus type 2 envelope are related with the dynamics of the neutralizing antibody response providing further support for a model in which Nabs play an important role in HIV-2 pathogenesis.

Chromosomal structure: a selectable trait for evolution

Dissertation presented to obtain the Ph.D degree in Evolutionary Biology

Intron evolution in primates

Dissertation presented to obtain a Ph.D degree in Evolutionary Biology

Intention recognition, commitment and their roles in the evolution of cooperation

Dissertação para obtenção do Grau de Doutor em Informática

Efetividade da intervenção conservadora e de um programa de exercício físico no solo na osteoartrose do joelho

RESUMO: Objectivo: O estudo do efeito da fisioterapia e do exercício em diversos indicadores relacionados com a osteoartrose do joelho tem evidenciado efeitos benéficos em utentes com esta condição. Nesta sequência, pretendeu-se avaliar a efetividade da intervenção conservadora em conjunto com um programa de exercícios ao nível da dor, rigidez, amplitude articular, função física e qualidade de vida em utentes com osteoatrose do joelho a curto prazo, quando comparado com a intervenção recomendada. A prática clínica atual em Portugal, sob prescrição, desenvolve-se de acordo com o padrão que se pretende investigar. Metodologia: Trata-se de um estudo quasi-experimental controlado e sem aleatorização. Os utentes da Clínica FPM (n=20; 35,0% homens, 65,0% mulheres) sujeitos à intervenção conservadora (calor húmido, ultra-som e massagem) em conjunto com um programa de exercício no solo, durante um período de 4 semanas com frequência diária, integram o grupo experimental e os utentes inscritos no programa de exercício a solo do “Viver Activo” no Leirisport (n=21; 23,8% homens, 76,2% mulheres), num período de 8 semanas com frequência bi-semanal são considerados como grupo de controlo. Os instrumentos de medida aplicados foram o Knee Outcome Osteoarthritis Score (KOOS) para os outcomes dor, rigidez, função física e qualidade de vida e a goniometria para a amplitude articular. Resultados: Em ambos os grupos foram observados aumentos significativos em todos os outcomes avaliados pelo KOOS (dor, rigidez, função física e qualidade de vida) e pela goniometria (amplitude articular) num período de 4 e 8 semanas. Quando comparada a evolução do grupo experimental com a do grupo controlo, verifica-se que as diferenças significativas ocorrem na flexão (p <0,05) (maior evolução para o grupo experimental), e na dor (p <0,05) (maior evolução para o grupo controlo). Nos outcomes rigidez, função física e qualidade de vida foi ainda possível identificar resultados positivos que sugerem possíveis benefícios da intervenção em grupo para os sujeitos a ela submetidos. Discussão e Conclusão: Estes resultados sugerem que a intervenção clínica individualizada é mais efectiva do que a intervenção em grupo no aumento da amplitude articular do joelho em utentes com osteoartrose a curto prazo. No entanto, para os outcomes dor, rigidez, função física e qualidade de vida, a intervenção em grupo parece ser clinicamente e estatisticamente melhor. A relevância deste estudo afirma-se ao demonstrar que utentes com osteoartrose do joelho que integrem um programa de exercício em grupo beneficiam de melhorias importantes. Ao adicionar sessões de fisioterapia para realização de intervenção conservadora individualizada e exercícios supervisionados agrega um maior alívio sintomático.-------- ABSTRACT: Study of physical therapy and exercise into several indicators associated to knee osteoarthritis has shown positive effects in subjects within this condition. According to the study it has been evaluated the effectiveness of a conservative intervention along with a exercise program directed to pain, stiffness, range of motion, physical function and quality of life of patients with knee osteoarthritis in a short term when compared with the recommended intervention. Under prescription the current clinical practice in Portugal is developed according to the pattern to investigate. Methodology: This is a quasi-experimental controlled study without randomization. The subjects of FPM Clinic (n= 20, 35.0% men, 65.0% women) were submitted to the conservative intervention (hot pack, ultrasound and massage) with a land exercise program during a 4 week-period (all-weekly) were assigned in the experimental group. Patients signed in the land exercise program of "Active Living" in Leirisport (n = 21, 23.8% men, 76.2% women) a 8 week-period (bi-weekly) were assigned as control group. Outcomes were measured by the Knee Outcome Osteoarthritis Score (KOOS) for pain, stiffness, physical function and quality of life. Goniometry was used for range of motion. Results: Both treatment groups obtained successful outcomes measured by significant reductions in KOOS scores and improvement in goniometry in a 4 and 8-week period. When compared the evolution of the experimental group with the control group it appears that significant differences occur in the range of motion (p <0.05) (further progress in the experimental group), and pain (p <0.05) (further evolution for the control group). In outcomes stiffness, physical function and quality of life was possible to identify positive results that suggest potential benefits of intervention for the submitted subjects. Discussion and Conclusion: These results suggest that individualized clinical intervention is more effective than group intervention in range of motion improving in patients with knee osteoarthritis in a 4-week period. However outcomes for pain, stiffness, physical function and quality of life appear to be clinically and statistically better for the group intervention. The significance of this study is essencial because it demonstrates that patients with knee osteoarthritis who incorporate an exercise program in group reveal improvements. When adding physical therapy sessions with individual conservative intervention and supervised exercises the result is an improvement of symptomatic relief.

Human mucocutaneous leishmaniasis in Três Braços, Bahia - Brazil: an area of Leishmania braziliensis braziliensis transmission. II. Cutaneous disease. Presentation and evolution

The clinical records of 182 patients with cutaneous leishmaniasis probably due to Leishmania braziliensis braziliensis are analysed. 68% had a single lesion which was usually an ulceron the lower anterior tibial third. Many had short histories of one to two months and all age groups were represented 13% had closed lesions of a verrucose or plaque like nature. Evolution of these skin lesions after treatment was related to the regularity of antimony therapy. Although healing usually occurred in three months, the time to scarring after commencing treatment was variable and related to the size ofthe lesion (p < 0.01). Usually if sufficient antimony treatment was given the lesion closed. Seven of the ten patients with initially negative leishmanin skin tests converted to positive after treatment. A significant decline of indirect fluorescent antibody titres occurred in patients followed, during and after therapy.

Evolution of sarcoma 180 (ascitic tumor) in mice infected with Schistosoma mansoni

Mice infected with 60 cercariae of Schistosoma mansoni were more resistant to the sarcoma 180 ascites tumor. Tumor inoculation was performed 50 days after schistosoma infection and the animals were observed and weighed at 48 hours intervals for development and progression of malignancy. In infected mice the weight gain (ascites formation) started later and was shorter than in uninfected Controls. Also, the number of tumor cells into the peritoneal cavity 72h after tumor implantation was shorter in infected group than incontrols. This in creased resistance against a transplantable tumor probably is related to the effect of endotoxin on tumoricidal activity of macrophages activated by the infection. The immunodepression induced by Schistosoma mansoni infection enhances the proliferation of endogenous bacteria increasing the amount of endotoxin absorbed from the gut.

Evolution in public procurement and the impact of e-procurement platforms: A case study

A Work Project, presented as part of the requirements for the Award of a Masters Degree in Management from the NOVA – School of Business and Economics