Síndrome de Guillain-Barré em associação temporal com a vacina influenza A / Guillain-Barré syndrome in temporal association with influenza A vaccine

OBJETIVO:Descrever um caso de síndrome de Guillain-Barré em associação temporal com a vacina influenza A (H1N1) 2009. DESCRIÇAO DO CASO: Menino de quatro anos com queixa inicial de dor em coxa direita e perda de força muscular ascendente 15 dias após a segunda dose da vacina influenza A (H1N1) 2009. Ao exame neurológico apresentava tetraparesia e arreflexia, com predomínio em membros inferiores. A eletroneuromiografia evidenciou redução da velocidade e bloqueio de condução neuronal, com discreta perda axonal secundária. Foi tratado com imunoglobulina por via intravenosa, atingiu platô no quarto dia de evolução da doença e, depois, houve melhora progressiva da força muscular. COMENTÁRIOS: Com o emprego em larga escala da vacina influenza A (H1N1) 2009 em nosso meio e os dados preliminares do sistema de vigilância norte-americano mostrando associação temporal significante com a síndrome de Guillain-Barré, recomenda-se a descrição dos casos suspeitos dessa associação. A vacina continua sendo o método mais efetivo para prevenir doença grave e morte por influenza.

OBJECTIVE: To report a case of Guillain-Barré syndrome following influenza A (H1N1) 2009 vaccine. CASE DESCRIPTION: A four-year-old boy presented right thigh pain and ascending muscular weakness 15 days after the second dose of influenza A (H1N1) 2009 vaccine. The neurological examination revealed tetraparesis and areflexia. Electroneuromyography showed lower velocity and conduction blockage with small secondary axonal loss. Treated with intravenous immunoglobulin, the patient reached a plateau in the 4th day, followed by progressive muscular strength improvement. COMMENTS: The employment of large-scale influenza A (H1N1) 2009 vaccination and the preliminary reports from the American Surveillance Program suggest a significant association between Guillain-Barré syndrome and influenza A H1N1 2009 vaccination. All suspected cases of this association should be published for further evaluation. Vaccination remains the most effective method to prevent serious illness and death related to influenza.

Prolonged use of tenofovir in HIV/hepatitis B virus (HBV)-coinfected individuals does not lead to HBV polymerase mutations and is associated with persistence of lamivudine HBV polymerase mutations.

OBJECTIVES: The aim of the study was to identify and characterize hepatitis B virus (HBV) polymerase gene mutations associated with ongoing HBV replication in HIV/HBV-coinfected individuals receiving tenofovir (TDF). METHODS: This retrospective cross-sectional study identified 28 HIV/HBV-coinfected individuals who had received TDF for at least 3 months. All patients had samples available while receiving TDF (on-TDF), and 24 also had samples available prior to treatment (pre-TDF). Case records were reviewed to obtain clinical and virological data at the times of sampling (+/-3 months). The HBV DNA of all samples was amplified using polymerase chain reaction (PCR), and the polymerase region of PCR-positive samples was sequenced and compared with reference HBV data. RESULTS: Of the pre-TDF samples, 15 of 24 (63%) were HBV PCR positive. Of the on-TDF samples, four of 28 (14%) were HBV PCR positive (mean time on TDF 13.5 months; range 3-23 months). Lamivudine (3TC)-resistance mutations were detected in three of four (75%) of these viraemic samples. The previously identified putative TDF-resistance mutations, rtA194T+rtL180M+rtM204V, were not detected in any individual. CONCLUSIONS: Unique mutations in the HBV polymerase gene associated with TDF resistance are rare in HIV/HBV coinfection. 3TC-resistance mutations persist and a significant proportion of patients are HBV PCR positive despite the addition of TDF.

Clinical significance of precore and core promoter mutations in genotype D hepatitis B-related chronic liver disease.

SUMMARY: The impact of mutations in the precore and basal core promoter (BCP) regions of the hepatitis B virus on the course of chronic liver disease is not well established. We sought to examine the relationship of these characteristics to the clinical expression of liver disease in patients infected with genotype D chronic hepatitis B (CHB). BCP and precore mutations in 110 patients with genotype D1 CHB were determined and correlated with clinical phenotype. Of 110 patients, 95 (86.5%) were HBeAg-negative. Compared with HBeAg-positive subjects, HBeAg-negative patients were over a decade older and had lower viral loads (3.70 +/- 0.98 vs 5.77 +/- 0.69 log copies/ml, P < 0.001). The double mutation A1762T-G1764A was more prevalent in patients with advanced liver disease (AdLD) and was associated with higher alanine aminotransferase and viral load. After adjusting for age, there was a more than fourfold increase in the risk of AdLD with this mutation (OR = 4.4; 95% CI: 1.13-16.92, P < 0.03). Conversely, the G1757A substitution was associated with protection, being 90% less frequent among patients with AdLD (P = 0.001). The results indicate that in genotype D CHB, the presence of the A1762T-G1764A mutation was associated with more aggressive liver disease while the G1757A substitution was associated with protection from advanced disease.

Chronic hepatitis B: recommendations for therapy based on the natural history of disease in Australian patients.

BACKGROUND: Chronic hepatitis B infection (CHB) is a major health problem in Australia and worldwide. CHB is associated with significant long-term morbidity and mortality. Well tolerated treatment is now available, however the development of resistance is common and the optimal timing of treatment is yet to be determined. Identifying the factors that influence the natural history of CHB may help determine which patients need treatment and when to start it. OBJECTIVE: To determine the demographics, clinical features and virological profile of Australian patients infected with CHB and the influence of these factors on disease activity and severity. STUDY DESIGN: Review of prospectively collected demographic, clinical and virological features of all patients positive for hepatitis B surface antigen (HBsAg) for more than 6 months who were referred to St. Vincent's Hospital liver clinics. Age, sex and ethnicity were correlated with hepatitis B e antigen status (HBeAg), HBV replication status (ALT and HBV DNA), genotype and liver histology. RESULTS: 703 chronic hepatitis B surface antigen positive patients were identified. The patients were predominantly male with an average age of 44. Eighty two percent of patients were born overseas, primarily from Asian (65%) and Mediterranean countries (14%). Two thirds (426) had an elevated ALT (median 79) at presentation. HBeAg was positive in 37%. Active viral replication, defined as abnormal ALT or positive HBVDNA, was present in 74%, 48% of whom were HBeAg negative. In a subset of 103 patients genotyped, 8% had genotype A, 29% B, 41% C and 22% D. Genotype correlated with ethnicity; patients infected with genotypes A were predominantly Caucasian, B and C were Asian, and D were Mediterranean. Of 296 (42%) patients who underwent liver biopsy, 76 (27%) had advanced fibrosis. Advanced fibrosis was associated with increasing age and Mediterranean ethnicity. CONCLUSION AND RECOMMENDATIONS: Perinatal or early childhood transmission is predominant mode of infection in Australia. Two thirds of this cohort had active replication and were at increased risk of developing cirrhosis and/or hepatoma. Advanced disease was associated with age and ethnicity. HBeAg negative CHB accounts for almost half of all those with active viral replication. This parallels the rise in this form of CHB in Asia and the Mediterranean basin. Screening should be offered to people born in, or with parents born in areas of high endemnicity. To detect the development of active disease, patients with positive HBsAg but normal ALT should have liver function tests done 6 monthly and those with elevated ALT should be referred for consideration of therapy, irrespective of HBeAg status.

Clinical emergence of entecavir-resistant hepatitis B virus requires additional substitutions in virus already resistant to Lamivudine.

Entecavir (ETV) exhibits potent antiviral activity in patients chronically infected with wild-type or lamivudine (3TC)-resistant (3TC(r)) hepatitis B virus (HBV). Among the patients treated in phase II ETV clinical trials, two patients for whom previous therapies had failed exhibited virologic breakthrough while on ETV. Isolates from these patients (arbitrarily designated patients A and B) were analyzed genotypically for emergent substitutions in HBV reverse transcriptase (RT) and phenotypically for reduced susceptibility in cultures and in HBV polymerase assays. After 54 weeks of 3TC therapy, patient A (AI463901-A) received 0.5 mg of ETV for 52 weeks followed by a combination of ETV and 100 mg of 3TC for 89 weeks. Viral rebound occurred at 133 weeks after ETV was started. The 3TC(r) RT substitutions rtV173L, rtL180M, and rtM204V were present at study entry, and the additional substitutions rtI169T and rtM250V emerged during ETV-3TC combination treatment. Reduced ETV susceptibility in vitro required the rtM250V substitution in addition to the 3TC(r) substitutions. For liver transplant patient B (AI463015-B), previous famciclovir, ganciclovir, foscarnet, and 3TC therapies had failed, and RT changes rtS78S/T, rtV173L, rtL180M, rtT184S, and rtM204V were present at study entry. Viral rebound occurred after 76 weeks of therapy with ETV at 1.0 mg, with the emergence of rtT184G, rtI169T, and rtS202I substitutions within the preexisting 3TC(r) background. Reduced susceptibility in vitro was highest when both the rtT184G and the rtS202I changes were combined with the 3TC(r) substitutions. In summary, infrequent ETV resistance can emerge during prolonged therapy, with selection of additional RT substitutions within a 3TC(r) HBV background, leading to reduced ETV susceptibility and treatment failure.

Does GH replacement therapy in adult GH-deficient patients result in recurrence or increase in size of pituitary tumours?

OBJECTIVE: Hypopituitary GH-deficient patients have an increased cardiovascular mortality and GH replacement in this population has resulted in considerable therapeutic benefit. GH replacement involves administration of a potentially mitogenic substance to patients with a previous or residual pituitary tumour. Our objective was to evaluate whether GH replacement results in an increase in the size of pituitary tumours. METHODS: This was a non-randomised observational study on patients recruited from the endocrine clinic. All subjects had GH deficiency, proven on an insulin tolerance test and were divided into those who were or were not receiving long-term GH replacement. Comparison of change in pituitary size was made with interval radiological imaging of the pituitary. RESULTS: Seventy-five patients (40 men and 35 women) were in the study, 47 were on long-term GH replacement and there were 28 controls. The average length of treatment for the treated group was 3.6 patient years. Thirty-nine patients in the treated group had at least 2 years of GH treatment between imaging studies of the pituitary. Two patients in the treated group had an increase in pituitary size (non-functioning adenomas) and two in the control group (one functioning and one non-functioning adenoma adenoma). None of these four patients required further treatment. There was no statistically significant difference between the two groups. CONCLUSION: Using a representative cohort of hypopituitary patients attending an endocrine clinic, GH replacement was not associated with an increased pituitary tumour recurrence rate. Although the results are not conclusive, in the period of observation GH had little adverse effect but longer studies are required to be certain.

Voluntary screening program for HIV in pregnancy. Cost effectiveness.

OBJECTIVE: To determine the effectiveness of a voluntary human immunodeficiency virus (HIV) screening program in pregnancy. STUDY DESIGN: Using a business decision theory analysis model, we estimated the outcomes and costs of the two possible decisions by our patients (test/no test). Patients with a positive HIV screen would undergo evaluation and possible prophylactic antiviral therapy. The model was utilized to evaluate the Naval Medical Center San Diego Program from 1995-1997. RESULTS: Prevalence of HIV in active duty Navy personnel during the years evaluated were 1995, 0.024%; 1996, 0.028%; and 1997, 0.022%. Patients screened for HIV during these years were 1995, 3,874; 1996, 3,924; and 1997, 4,127 (n = 11,925). Incidence of HIV seroprevalence in patients screened during the study period was zero. The number of patients declining HIV screening was: 1995, 10; 1996, 8; and 1997, 5. During the same period, reported HIV seroprevalence among pregnant patients in the United States was 1.5/1,000. CONCLUSION: HIV seroprevalence in our pregnant population (zero) was lower than expected, considering the national pregnancy prevalence and Navy prevalence. The expected number of cases of positive HIV screens was 17.8. The cost of the program for the study period was $103,748. The cost of care for one positive neonate ranges between $100,000 and $200,000.

Influence of mood and adjustment to cancer on compliance with chemotherapy among breast cancer patients.

Approximately 75% of the 181,000 breast cancer patients newly diagnosed in 1992 will survive for at least 5 yr, but survival often depends on receiving adjuvant chemotherapy. We determined that mood variables and attitude toward cancer could predict compliance with IV-administered chemotherapy. The participants were seventy-four women diagnosed with primary breast cancer receiving treatment at a state-supported medical center in one of three southeastern metropolitan areas in the U.S. Most patients were members of minority and lower socioeconomic groups. The design was prospective in the sense that mood and attitude variables were assessed before determination of compliance. Two psychological instruments were used in this study, the Mental Adjustment to Cancer (MAC) Scale and the Affects Balance Scale (ABS). Patients who kept fewer than 85% of their appointments were classified as noncompliant; those keeping 85% or more were classified as compliant. Sixty-three percent of the patients for whom the compliance information was complete were classified as compliant; 37% were noncompliant; and four patients were not included in the analysis because their records were incomplete. The discriminant function was able to correctly classify 86% of the patients according to chemotherapy compliance, a 36% improvement over the chance level. High scores on MAC Fighting Spirit and ABS Anxiety, Depression, and Vigor scales were associated with greater adherence to a chemotherapy regimen. High scores on ABS Guilt and Hostility scales predicted lower levels of compliance.

Inhibition of IFN-gamma induction of class II MHC genes by cAMP and prostaglandins.

Triggering of the cyclic AMP (cAMP) signal transduction pathway inhibits the the interferon gamma (IFN-gamma)-mediated induction of class II major histocompatibility (MHC) genes. We have investigated the mechanism of the inhibition of IFN-gamma induction of the murine A alpha class II MHC gene by cAMP and E series prostaglandins (PGEs). 151 base pairs of the A alpha promoter were sufficient to confer positive regulation by IFN-gamma and negative regulation by cAMP which accurately mirrored the regulation of the endogenous A alpha gene. cAMP also inhibited the IFN-gamma activation of the Fc gamma receptor I (Fc gamma RI) gene promoter, an "early" promoter which is activated immediately after treatment of cells with IFN-gamma. PGEs, which cause an elevation in intracellular cAMP, inhibited the induction of the A alpha promoter, and inhibition was greater in the presence of tumor necrosis factor alpha (TNF alpha). A mutational analysis of the A alpha promoter showed that all four conserved class II promoter elements, the S, X1, X2, and Y boxes, play a role in mediating A alpha promoter activation by IFN-gamma. Mutations in these elements did not diminish the cAMP inhibition of promoter activation by IFN-gamma. Thus, conserved class II promoter sequences which mediate most known examples of positive and negative regulation, including cAMP inhibition of constitutive class II expression, do not mediate cAMP inhibition of IFN-gamma activation of the A alpha promoter. We suggest that this inhibition may be mediated by a novel class II promoter element or by disruption of an early step in the IFN-gamma signal transduction pathway.

Possible pubertal effect on therapeutic gains in an autistic girl.

A deaf, partially sighted, severely retarded autistic girl, 11 years, 6 months of age, received approximately 2 years of occupational therapy, where sensory integration procedures were employed to reduce self-stimulation. Videotaped time samples of the amount of stereotypies showed a consistent reduction from the time of starting therapy to an interruption for vacation and surgery for scoliosis 46 weeks later. On returning to therapy after a 9-week break, self-stimulation had greatly increased and did not return to the presurgery level during an additional 55 weeks of therapy, 30 of which followed the removal of a cast. Menarche occurred 1 week after removing the cast. Increased self-stimulation is linked to reduced inclination toward environmental interaction as well as to an interruption of intervention and possible pubertal effect. Brief reports on four other autistic adolescents who received similar therapy are consistent with the conjecture of frequent pubertal regression.

Acromegaly caused by pulmonary carcinoid tumours.

Two patients are described whose acromegaly was cured by removal of a bronchial carcinoid tumour. One had an enlarged pituitary fossa and evidence is presented that in this patient the tumour was not secreting growth hormone. The evidence available suggests that the tumour was producing a growth hormone releasing substance. It is suggested that some cases of the pluriglandular syndrome may be secondary to small bronchial carcinoid tumours that produce substances as yet unidentified, that stimulate the growth and hyperactivity of other endocrine tissue.