First evaluations of LPV/RTV (Kaletra) efficacy on HIV-positive patients treated with multiple drugs

At the current epidemic stage, characterized by the rise of antiretroviral drug resistance, it is necessary to administer to HIV-positive patients increasingly effective treatments. This is possible only by means of powerful drugs. In a retrospective study, the authors evaluate 78 patients: 76 pre-treated with multiple drugs and 2 na ves. The 78 patients received LPV/RTV, starting from the fourth 3-month period of 2000 until the first 3-month period of 2002. The average treatment duration was 6.5 ( 5.5) months; the median value 6 months. The efficacy of the LPV/RTV therapeutic regimen was evaluated by a cytofluorimetric count of CD4+ and determination of the HIV viral load. There were 14 drop-out patients (17.9%): 5 because of auto-suspension, 1 due to absence of clinical and virological efficacy, 5 due to side effects (3 hepatopathy, 1 allergy and 1 nausea); three patients were lost on follow-up. There were 64 (82.1%) patients on treatment. Forty patients responded (51.3%) and 13 (16.7%) had uncontrolled viraemia (over than 200 copies/ml). However, the treatment with LPV/RTV was not interrupted for these patients, because in the follow-up they showed an increase in CD4+ values. The authors conclude that the LPV/RTV combination confirms previous findings: it is a drug with a relatively low incidence of side effects, capable of powerful results even in the treatment of patients receiving multiple drugs and thus subjected to the risk of developing antiretroviral drug resistance.     

Genetic heterogeneity of small ruminant lentiviruses involves immunodominant epitope of capsid antigen and affects sensitivity of single-strain-based immunoassay

The pol and gag gene fragments of small ruminant lentivirus field isolates collected in the last decade in Italy were amplified, sequenced, and analyzed. Phylogenetic analysis revealed that the majority of ovine isolates form a distinct cluster more similar to caprine lentivirus prototypes than to the visna virus prototype. These findings confirm and extend those reported by Leroux et al. (Arch. Virol., 142:1125-1137, 1997). Moreover, we observed that a variable region of Gag, included in the fragment analyzed, corresponded to one of the three major capsid antigen epitopes, which suggests that the antibody response to this epitope may be type specific. To test this hypothesis, two recombinant peptides, derived from the Icelandic prototype K1514 and this novel genotype, were expressed and used in an enzyme-linked immunosorbent assay to screen a panel of ovine and caprine sera collected from different geographical locations in Italy. Several sera reacted in a type-specific manner, indicating that in a diagnostic setting the combination of at least these two type-specific peptides is necessary to cover a wide range of infections. Additionally, these results support the hypothesis of cross-species transmission based on the phylogenetic analysis described above. This has implications for the control and eradication of small ruminant lentivirus infections.     

Sarcomatoid carcinoma of the urinary tract

Sarcomatoid carcinoma is a rare variant of malignant tumor arising from the urinary tract. This tumor had been termed carcinosarcoma because of its carcinomatous and sarcomatous components. There is still some confusion in the terminology between true carcinosarcoma and sarcomatoid carcinoma; however, the latter is now regarded as primarily a malignant epithelial tumor with pseudosarcomatous transformation.
Four cases of sarcomatoid carcinoma arising from the urinary tract are reported. The patients were a 77 year old female, and three males aged 62, 69 and 80 years. All but the eldest patient complained of gross hematurla. Surgical removal was performed in the younger three cases, and an autopsy was done in the remaining case. All the tumors were macroscopically polypoid. Histopathologic examination revealed fasciculated spindle-cell tumors with myxold stroma or malignant fibrous histiocytoma-like spindle cell tumors. The epithelial nature was proven in these sarcomatous cells by immunohistochemical andlor electron-microscopic examinations. Only a small amount of squamous cell carcinoma components was also evident in the latter three cases. Although the younger three patients were alive at 44, 23 and 39 months'follow-up, respectively, constant careful monitoring Is recommended.     

Immunohistochemical and serological 90K/Mac-2BP detection in hepatocellular carcinoma patients: different behaviour of two monoclonal antibodies

To clarify the biological role of the 90K/Mac-2BP glycoprotein, we evaluated the ability of two MAbs SP-2 and 1A4.22, to reveal this glycoprotein in both serum and tissue from hepatocellular carcinoma (HCC) patients. Tissue expression of 90K was detected by the immunohistochemical method in 20 HCC patients, while the 90K serum level was assessed by the ELISA assay in 13 HCC patients. MAb SP-2 was reactive only in serum, with a mean value of 12.8+/- 6.7 microg/ml . On the contrary, MAb 1A4.22 revealed immunoreactivity both in 92% of sera and in 60% of neoplastic samples. Positive staining was seen only in the epithelial cells and was cytoplasmic and granular in all instances. The mean 90K serum level assayed with MAb 1A4.22 was 29.4 +/- 13.7 microg/ml. Patients with a 90K serum level 30 microg/ml. Moreover, a possible poor prognostic role was observed for negative 90K in tissue. Our results suggest that only MAb 1A4.22 could demonstrate 90K glycoprotein expression in paraffin-embedded tissue and that this MAb could have a diagnostic and prognostic role in both sera and tissues from HCC patients.     

Visual perception in women during the menstrual cycle

Twelve females were tested at four times during the menstrual cycle with a visual detection task and a visual pattern discrimination task. Mood levels and confidence ratings were evaluated for each session. In addition to the behavioral testing, plasma samples were collected and radioimmunoassayed for estradiol, progesterone, luteinizing hormone, and follicle stimulating hormone levels. Visual detection fluctuated significantly during the menstrual cycle with impaired performance occurring at the premenstrual session. In contrast to previous reports, the impaired performance was not related to lowered confidence ratings or to mood levels.     

Blood and Marrow Transplant Clinical Trials Network State of the Science Symposium 2007.

Outcomes of hematopoietic cell transplantation are steadily improving. New techniques have reduced transplant toxicities, and there are new sources of hematopoietic stem cells from unrelated donors. In June 2007 the Blood and Marrow Transplant Clinical Trials Network convened a State of the Science Symposium of more than 200 participants in Ann Arbor to identify the most compelling clinical research opportunities in the field. This report summarizes the symposium's discussions and identifies eleven high priority clinical trials that the network plans to pursue over the course of the next several years.     

Carrier detection in Duchenne and Becker muscular dystrophy Argentine families

In order to offer carrier detection, genetic counseling, and prenatal diagnosis to families with Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) in our country, segregation analysis of highly polymorphic short tandem repeats (STR) (dC-dA)n: (dG-dT)n loci was utilized. The risks to females of 15 DMD/BMD families (9 familial and 6 sporadic) were evaluated on STR, pedigree and serum creatine kinase (SCK) data. From the 36 females at risk of being carriers (not including 8 obligate carriers), results of STR analysis were compatible with carrier status in 7 and not compatible in 20. In 9 females, no information regarding carriership was derived from the STR analysis. Prenatal diagnosis is now possible on the carrier females. Previously identified deletions in the central part of the gene were confirmed by STR analysis in 3 families. Five new alleles were identified in Argentine individuals; allele frequencies differed from those of North American people. Results derived from this study are useful for carrier detection and genetic counseling in DMD/BMD. One case of probable mosaicism in an unaffected father was detected on a pedigree basis in a family with DMD patients.     

Bruton tyrosine kinase gene mutations in Argentina

The block in differentiation from pro-B to pre-B cells results in a selective defect in the humoral immune response characteristic of human X-linked agammaglobulinemia (XLA). Mutations of Bruton tyrosine kinase (BTK) gene have been identified as the cause of XLA. Mutation detection is the most reliable method for making a definitive diagnosis, except when clinical and laboratory findings are distinctive and coupled with history of X-linked inheritance. To provide a definitive diagnosis to 40 families incorporated in the Argentinian Primary Immunodeficiencies Registry we analysed the BTK gene by SSCP analysis as screening method for XLA, followed by direct sequencing. The molecular defect was localized in 45 patients from 34 unrelated families. From the 34 independent mutations identified, 16 were previously undescribed, 31 were unique mutations, 22 were exonic single nucleotide changes (16 missense and 6 nonsense) and four intronic mutations. Because five families had clinical, immunological and inheritance data sufficient for a definitive diagnosis, our study allowed 37 patients from 29 families previously categorized probable/ possible XLA, have now definitive diagnosis leading to appropriate genetic counseling.     

Polymorphisms in the methylenetetrahydrofolate reductase and methionine synthase reductase genes and homocysteine levels in Brazilian children

Hyperhomocysteinemia is a risk factor for thrombosis, and methylenetetrahydrofolate reductase (MTHFR) and methionine synthase reductase (MTRR) polymorphisms, folate, and B12 levels could contribute to plasma homocysteine (Hcy) variation. Although well established in adults, few studies have been performed in childhood. In this study, we investigated association of polymorphisms C677T and A1298C in the MTHFR gene and A66G in the MTRR gene with Hcy levels in children. These polymorphisms, as well as Hcy, folate, and vitamin B12 levels were investigated in 220 normal children with ages ranging from 1 to 8 years. Plasma Hcy, folate, and vitamin B12 levels were normal in all children. None of the polymorphisms could be considered an independent risk factor for hyperhomocysteinemia during childhood. The median Hcy levels in 37 children (17%) doubly heterozygous for C677T and A1298C mutations in the MTHFR gene were not different from the other genotypes. However, the association of the different genotypes with Hcy, folate, and vitamin B12 levels demonstrated significant P-values. The folate levels demonstrated a statistically significant decrease (P = 0.0477) from the C677T mutation in the MTHFR gene (TT genotype) when compared to the other groups. Folate was the only independent risk factor for hyperhomocysteinemia. Thus, monitoring the concentrations of folate would be more helpful for evaluating hyperhomocysteinemia and for preventing cardiovascular disease.