Tuberculosis in Italian and non-EU patients. Review of case mix (1996-2001)

The Authors examined the case mix of patients with tuberculosis who were hospitalised from 1996 to the first 6 months of 2001 at the Infectious Disease Department. The patient population comprises two groups with different epidemiological characteristics. The first group consists of Italians [62] and the second of Non-EU patients [28]. The Italians have an older average age and their epidemiological and clinical risks are more serious in comparison to Non-EU's. Moreover, among Italian patients the number of subjects with HIV infection is greater. The presence of tuberculosis at the lymph nodes appears to be related to patients with HIV, whereas for HIV-negative patients the most frequent sites are the lungs and pleura. Some of the patients underwent biopsy in the sites affected by the pathology and the histopathological findings are very similar to the typical data. There does not seem to be any difference between the results of the X-rays of the lung X-rays for the Italians and the Non-EU's, whereas in general there are very few patients who show the typical location of tuberculosis at the apex of the lungs.     

Comparison between rules-based human immunodeficiency virus type 1 genotype interpretations and real or virtual phenotype: concordance analysis and correlation with clinical outcome in heavily treated patients

We compared 2 rules-based genotype interpretation systems and real or virtual phenotype through a retrospective analysis of a prospective trial. Genotypes were determined with VircoGEN II (VIRCO) and were interpreted with either RetroGram 1.4 or TRUGENE HIV-1 (guidelines 3.0) or original virtual phenotype (Virtual Phenotype; VIRCO), as available in the year 2000. Among 188 human immunodeficiency virus (HIV) type 1 isolates, overall concordance (kappa agreement) was observed for the 2 rules-based systems, whereas striking discordances were noted between them and real and virtual phenotype interpretations for stavudine, didanosine, zalcitabine, abacavir, and amprenavir (kappa<0.4). Clinical evaluation of a subset of 173 patients showed that both rules-based sensitivity scores were independently associated with HIV RNA loads <400 copies/mL at week 16 of during-treatment analysis (TRUGENE: odds ratio [OR], 2.90; 95% confidence interval [CI], 1.52-5.52; P=.001; RetroGram: OR, 2.34; 95% CI, 1.21-4.55; P=.012), whereas, in contrast to real or virtual phenotype, interpretations according to biological cut-offs were not (OR, 1.91; 95% CI, 0.77-4.76; P=.162).     

Lopinavir plasma concentrations and changes in lipid levels during salvage therapy with lopinavir/ritonavir-containing regimens

OBJECTIVE: To determine whether an association existed between lopinavir (LPV) plasma concentrations and changes in lipid levels. DESIGN: A prospective, nonrandomized study. SUBJECTS: HIV-infected subjects with virologic failure on protease inhibitor-containing regimens. Twenty-two consecutive patients were enrolled, 19 completed 24 weeks of treatment, and 16 completed the full 48-week study period.INTERVENTION Patients were treated with LPV/ritonavir (LPV/r) in combination with other antiretroviral agents. Subjects were evaluated at baseline and weeks 4, 8, 12, 24, 36, and 48. LPV trough plasma concentrations and lipid levels were measured. RESULTS: LPV trough concentrations were higher in patients experiencing grade 3 or higher lipid elevations (mean [SD]: 9.71 microg/mL (5.62) vs. 6.09 microg/mL (3.83); P = 0.002) and in those developing grade 2 or higher hypercholesterolemia (mean [SD]: 8.48 microg/mL [4.64] vs. 5.71 microg/mL [3.94]; P = 0.003). All patients developing grade 2 or higher cholesterol elevation had an LPV trough concentration at week 4 greater than 8 microg/mL. Significant positive correlations were found between LPV trough concentrations and changes in triglyceride and cholesterol levels. CONCLUSIONS: In patients receiving salvage therapy with LPV/r, there is an association between LPV plasma concentrations and lipid changes. Patients achieving higher LPV trough concentrations may be at greater risk of experiencing dyslipidemia. Further investigations are warranted to support a direct cause and effect relationship.     

Evaluation of Toxoplasma gondii recombinant proteins for the diagnosis of recently acquired toxoplasmosis by an immunoglobulin G analysis

The value of T. gondii recombinant antigens rRop2, rGra4, rGra7 and rSAG1m (mature version) or rSAG1ct (C-terminal version) in differentiating recently acquired from chronic infections was determined by IgG-ELISA. The general highest sensitivity was observed with rRop2 whereas rSAG1m was not recognized by any of the serum samples, suggesting an incorrect folding. rGra4 and rGra7 showed significant higher sensitivity and absorbance values with serum samples from recently infected individuals compared to those with chronic infection. In contrast, rRop2 and rSAG1ct did not show differences in the reactivity pattern between both groups of serum samples.     

Should patients with polycystic ovary syndrome be treated with metformin? Benefits of insulin sensitizing drugs in polycystic ovary syndrome--beyond ovulation induction

The debate on metformin use in polycystic ovary syndrome (PCOS) has mainly focused on its treatment for infertility in ovulation induction and menstrual cyclicity. Here we will summarize the data supporting the effect of metformin on improving hyperandrogenaemia and hyperinsulinaemia in PCOS patients. We propose that metformin benefits PCOS patients undergoing gonadotrophin therapy and IVF as well as ovulation induction. We also advocate the use of insulin sensitizing drugs to reduce miscarriage rates, and risks associated with coronary artery disease, gestational diabetes and obesity.     

Birth of two babies using oocytes that were cryopreserved in a choline-based freezing medium

BACKGROUND: Oocyte cryopreservation may have significant potential for assisted reproductive technology. However, to date, successful results have been limited. We report a preliminary series of IVF outcomes after fertilization of oocytes that were frozen in a low-sodium medium. METHODS: In this retrospective analysis, 12 patients (21-41 years old), who underwent IVF in a fertility clinic affiliated to the University of Buenos Aires, had oocytes cryopreserved in a modified phosphate buffered saline medium, in which sodium chloride was replaced by choline chloride. A slow-freezing, rapid-thawing protocol was used and oocytes were inseminated by ICSI. Outcome measures included oocyte survival, fertilization, implantation and pregnancy rates. RESULTS: Median oocyte survival was 63%. Median fertilization rate was 59%. Overall implantation rate was 25%. Six clinical pregnancies were achieved; two of these pregnancies went to term resulting in the birth of two babies. CONCLUSIONS: To the best of our knowledge, these are the first pregnancies and normal births using oocytes that were cryopreserved in a choline-based medium. The small sample size prevents us from concluding that freezing in a low-sodium medium is superior to using a conventional one.     

In vitro susceptibility to infection with SIVcpz and HIV-1 is lower in chimpanzee than in human peripheral blood mononuclear cells

This study was undertaken to evaluate and compare the susceptibility of chimpanzee versus human peripheral blood mononuclear cells (PBMCs) to infection with SIVcpz and HIV-1 non-syncitium inducing primary isolates. The results demonstrate clearly that chimpanzee PBMCs have a lower capacity to support viral replication as compared to human PBMCs. There was no experimental evidence that this difference was due to a lower availability of target cells for viral infection (PBMCs positive for CD4 and CCR5 molecules) or to a differential susceptibility to apoptosis (PBMCs positive for CD4 and CD95 molecules). A lower capacity of chimpanzee PBMCs to support SIVcpz and HIV-1 replication in vitro is related to a post-entry barrier to virus replication.     

Sequencing of the GRIK1 gene in patients with juvenile absence epilepsy does not reveal mutations affecting receptor structure

Hereditary factors play a major role in the etiology of juvenile absence epilepsy (JAE) that is a common subtype of idiopathic generalized epilepsy (IGE). Sander et al. [1997: Am J Med Genet 74:416-421] reported an allelic association of JAE with the nine-copy allele of a tetranucleotide repeat polymorphism in the third intron of the kainate-selective GluR5 receptor gene (GRIK1) and supportive evidence for linkage of IGE to GRIK1 in families of JAE probands. These findings suggest that a major genetic determinant of GRIK1 confers susceptibility to JAE. Assuming that the GRIK1 tetranucleotide repeat polymorphism is unlikely to have functional relevance itself, we have sequenced the coding regions and regulatory sequences of the GRIK1 gene in eight JAE patients who carry the nine-repeat allele of the GRIK1 tetranucleotide repeat polymorphism to detect a putative functional GRIK1 mutation that is in linkage disequilibrium with the nine-repeat allele. Seven of them were derived from families showing positive evidence for linkage to GRIK1. Our mutation analysis of coding regions and splice junctions revealed only two silent polymorphisms (A522C and C1173T) out of the five SNPs present in public databases and no mutations affecting protein structure. No significant differences were found in the allele frequencies of the detected polymorphisms between the JAE patients and controls. High levels of sequence conservation were also found in the promoter, in the 5' and both the 3' untranslated regions and in the RNA secondary structure involved in the editing reaction. The results presented indicate that mutations in the coding sequences, in the intron-exon boundaries and in the main regulatory regions of the GRIK1 are not commonly involved in the etiology of JAE.