Mediastinal tumors: biopsy under US guidance

Percutaneous biopsies of mediastinal tumors were successfully performed under sonographic guidance in 14 of 21 patients. In 10 of 11 malignant lesions, malignancy was determined by means of cytologic and histologic examination of the specimens obtained. A histologic diagnosis was reached in seven patients with malignant mediastinal tumors, including all four cases of Hodgkin lymphoma. Mediastinal biopsy under sonographic guidance is a technically simple, rapid, and accurate procedure, but its application is limited to tumors of the anterior mediastinum.     

Intravenous digital subtraction renal angiography: use in screening for renovascular hypertension

Intravenous digital subtraction renal angiography (DSRA) has been compared with conventional angiography only in small, selected series of hypertensive patients. The authors prospectively examined with intravenous DSRA 94 patients at increased risk for renovascular hypertension and compared these studies with conventional angiography. A stenosis of at least one main renal artery was identified with intravenous DSRA in 22 patients and confirmed in 20 patients. No significant stenoses were seen with conventional angiography in any of the 64 patients in whom lesions were not seen with intravenous DSRA. Since inadequate DSRA studies were considered positive for renal artery stenosis, the sensitivity of intravenous DSRA was 100% (25 of 25); specificity, 93% (64 of 69); positive predictive value, 83% (25 of 30); and negative predictive value, 100% (64 of 64). The authors conclude that intravenous DSRA is a sensitive test for identifying stenosis of the main renal arteries and is appropriate to use as a screening test among patients at increased risk for renovascular hypertension.     

Clustered mutations in HIV-1 gag are consistently required for escape from HLA-B27-restricted cytotoxic T lymphocyte responses

The immune response to HIV-1 in patients who carry human histocompatibility leukocyte antigen (HLA)-B27 is characterized by an immunodominant response to an epitope in p24 gag (amino acids 263-272, KRWIILGLNK). Substitution of lysine (K) or glycine (G) for arginine (R) at HIV-1 gag residue 264 (R264K and R264G) results in epitopes that bind to HLA-B27 poorly. We have detected a R264K mutation in four patients carrying HLA-B27. In three of these patients the mutation occurred late, coinciding with disease progression. In another it occurred within 1 yr of infection and was associated with a virus of syncytium-inducing phenotype. In each case, R264K was tightly associated with a leucine to methionine change at residue 268. After the loss of the cytotoxic T lymphocyte (CTL) response to this epitope and in the presence of high viral load, reversion to wild-type sequence was observed. In a fifth patient, a R264G mutation was detected when HIV-1 disease progressed. Its occurrence was associated with a glutamic acid to aspartic acid mutation at residue 260. Phylogenetic analyses indicated that these substitutions emerged under natural selection rather than by genetic drift or linkage. Outgrowth of CTL escape viruses required high viral loads and additional, possibly compensatory, mutations in the gag protein.     

Ultrasonography of the thyroid during pregnancy

To discover whether pregnancy causes ultrasonically detectable changes in the thyroid, an ultrasound examination of the thyroid was performed repeatedly in 21 pregnant women with no history of thyroid disease. Seven patients were examined three times and 14 twice during the course of pregnancy. The size of the thyroid was estimated and the echogenicity assessed with respect to homogenicity and degree by comparison with the echogenicity of adjacent muscles. The results were compared with the results of a control group of healthy female volunteers. The mean volume of the thyroid increased slightly during the course of pregnancy. No changes in the echogenicity or echostructure were noted.     

Year in review in Critical Care, 2003 and 2004: respirology and critical care

We summarize all original research in the field of respirology and critical care published in 2003 and 2004 in Critical Care. Articles were grouped into the following categories to facilitate a rapid overview: pathophysiology, therapeutic approaches, and outcome in acute lung injury and acute respiratory distress syndrome; hypoxic pulmonary arterial hypertension; mechanical ventilation; liberation from mechanical ventilation and tracheostomy; ventilator-associated pneumonia; multidrug-resistant infections; pleural effusion; sedation and analgesia; asthma; and techniques and monitoring.     

Lack of strong immune selection pressure by the immunodominant, HLA-A*0201-restricted cytotoxic T lymphocyte response in chronic human immunodeficiency virus-1 infection.

Despite detailed analysis of the HIV-1-specific cytotoxic T lymphocyte response by various groups, its relation to viral load and viral sequence variation remains controversial. We analyzed HLA-A*0201 restricted cytotoxic T lymphocyte responses in 17 HIV-1-infected individuals with viral loads ranging from < 400 to 221,000 HIV RNA molecules per milliliter of plasma. In 13 out of 17 infected subjects, CTL responses against the SLYNTVATL epitope (p17 Gag; aa 77-85) were detectable, whereas two other HLA-A*0201 restricted epitopes (ILKEPVHGV, IV9; and VIYQYMDDL, VL9) were only recognized by six and five individuals out of 17 individuals tested, respectively. Naturally occurring variants of the SL9 epitope were tested for binding to HLA-A*0201 and for recognition by specific T cell clones generated from five individuals. Although these variants were widely recognized, they differed by up to 10,000-fold in terms of variant peptide concentrations required for lysis of target cells. A comparison of viral sequences derived from 10 HLA-A*0201-positive individuals to sequences obtained from 11 HLA-A*0201-negative individuals demonstrated only weak evidence for immune selective pressure and thus question the in vivo efficacy of immunodominant CTL responses present during chronic HIV-1 infection.     

Immune correlates of HIV control

The development of an effective HIV vaccine is still hampered by the lack of clearly defined immune correlates of HIV control. Although a number of immune markers have been associated over last years with relative viral control and slower HIV disease progression, these associations are oftentimes complicated by the causality dilemma that does not allow to directly assign cause or effect to the identified parameters. In addition, many of these immune markers may act in concert or represent surrogate makers for otherwise controlled HIV infection. This review will revisit the current knowledge of host genetic and immune markers and their associations with HIV control, particularly examining the roles of virus-specific T cells and humoral immune responses and testing their role as direct correlates of control.