Percutaneous deep vein arterialization: An emerging technique for no-option chronic limb-threatening ischemia patients

Chronic limb-threatening ischemia (CLTI), with characteristic ischemic rest pain, non-healing ulcers, or gangrene attributable to arterial occlusive disease, requires successful revascularization to minimize tissue loss. End-stage CLTI in particular, with occlusion of the pedal arteries, results in a lack of suitable targets for bypass and can result in failure of endovascular revascularization procedures, leaving no option for treatment other than amputation. With limb salvage as the primary goal, nontraditional revascularization techniques such as percutaneous deep vein arterialization (pDVA) may help minimize incidence of amputation. We present a case of a patient with no-option CLTI, at high risk of amputation who failed conventional endovascular revascularization attempts facing imminent major amputation. The limb was salvaged with a successful pDVA procedure.     

Use of well-defined HIV-derived epitopes to evaluate CD4(+) and CD8(+) T cell responses in patients with chronic HIV-1 infection treated with HAART

Highly active antiretroviral therapy (HAART) is associated with a dramatic clinical benefit to HIV-infected patients through significant plasma viremia reduction and CD4(+) T cells increase. In previous reports, HIV-specific CD4(+) and/or CD8(+) T cell responses have been studied separately during HAART; therefore the relationship between these two virus-specific populations is currently not well understood. In this study, both HIV-specific CD4(+) and CD8(+) T cell responses were investigated using a large panel of well-defined T cell epitope peptides in 24 HIV-1-infected patients undergoing HAART, with undetectable viral load and CD4(+) T cell count >/= 350/mm(3). One-third of the patients had CD4(+) T cells able to proliferate when exposed to HIV-1 protein fragments but only two patients displayed polyclonal responses. In addition the majority (78%) of HAART-treated patients displayed no or monospecific CD8(+) T cell responses and the phenotypic analysis of these HIV-specific CD8(+) T cells demonstrated the absence of terminally differentiated effectors. In conclusion, the experimental approach used in this study shows that CD4(+) T cell responses may persist during HAART but are not associated with strong CD8(+) T cell responses     

Exposure to an obesity-inducing diet early affects the pattern of expression of peroxisome proliferator, retinoic acid, and triiodothyronine nuclear receptors in the rat

Since evidence has appeared that alpha and gamma isoforms of the peroxisome proliferator receptors (PPARs) are involved in the regulation of triglyceride homeostasis and in the control of the differentiation of adipocytes that is required for the development of obesity, a large number of studies have investigated the physiologic role of nuclear receptors in the control of energy balance. The aim of this study was to determine the early effects of an obesity-inducing diet on the expression of PPAR alpha and gamma and other nuclear receptors such as all-trans retinoic acid receptor (RAR) and triiodothyronine receptor (TR), which all form functional heterodimers with a common partner, the 9-cis retinoic acid receptor (RXR). The experiment used a cafeteria diet where 60% of the energy was supplied as lipids. This diet was offered to young rats for 8 and 28 days and the expression of nuclear receptors was determined at the end of each experimental time period (1) in the liver by assaying the binding properties of RAR and TR and by quantifying mRNA levels of RAR beta, TR alpha(1)beta(1), RXR alpha, and PPAR alpha, and (2) in the white adipose tissue (WAT) by quantifying mRNA levels of RAR alpha, RXR alpha, TR alpha(1)beta(1), and PPAR gamma(2). After 8 days of cafeteria diet a significant decrease of RAR and TR maximal binding capacity (MBC) was observed in the liver (-20.1% and -35.0%, respectively, P <.05) and the level of the mRNA of RAR beta was significantly decreased (-17.4%, P <.05). After 28 days of cafeteria diet, the level of the mRNA of PPAR alpha and acyl-CoA oxidase (ACOX) was significantly increased (+54.5% and +37.8%, P <.01 and P <.05, respectively), whereas the MBC of RAR and TR was significantly decreased (-16.0% and -23.4%, P <.01), as were the mRNA levels of RAR beta and TR alpha(1) beta(1) (-28.5% and -32.0%, P <.05). The level of RXR alpha mRNA was unchanged. In WAT, the mRNA level of PPAR gamma(2) was significantly increased after 28 days of cafeteria diet (+49.5%, P <.05) and the mRNA levels of RAR alpha and TR alpha(1) beta(1) significantly decreased (-22.3% and -31.0%, P <.05). These results as a whole showed that a high-fat diet can induce early modifications in the pattern of expression of nuclear receptors in the liver and the WAT. These modifications could be compatible with an early adaptive phenomenon. Further investigations are necessary to better understanding the link between the modifications of the pattern of expression of these receptors and plasticity of adipose tissue leading to the onset of obesity.     

Pulmonary infection due to Mycobacterium szulgai

A 75-year-old man was admitted with cough, purulent sputum, fatigue and weight loss of 10 kg of some months' duration. His chest radiograph showed poorly defined opacities in the right lung. Eleven years before admission an epidermoid carcinoma of the right lung had been diagnosed and a right bilobar resection had been performed. The patient remained asymptomatic for 8 years. Cultures of 4 consecutive sputum samples were positive for mycobacteria that were identified as Mycobacterium szulgai by gas chromatography. A 6-month regimen of rifampin, isoniazid and pyrazinamide resulted in complete eradication of the mycobacterium. M. szulgai is an unusual pathogen in humans. In the English literature, only 35 cases of pulmonary disease have been reported. Its clinical and radiological characteristics are similar to tuberculosis but in contrast to the rest of the non-tuberculous mycobacteria, M. szulgai has shown in vitro and in vivo susceptibility to most primary antituberculosis drugs.     

In vitro activities of LTX-109, a synthetic antimicrobial peptide, against methicillin-resistant, vancomycin-intermediate, vancomycin-resistant, daptomycin-nonsusceptible, and linezolid-nonsusceptible Staphylococcus aureus

LTX-109 and eight other antimicrobial agents were evaluated against 155 methicillin-resistant Staphylococcus aureus (MRSA) isolates, including strains resistant to vancomycin and strains with decreased susceptibility to daptomycin and linezolid, by microdilution tests to determine MICs. Time-kill assays were performed against representative MRSA, vancomycin-intermediate S. aureus (VISA), and vancomycin-resistant S. aureus (VRSA) isolates. LTX-109 demonstrated a MIC range of 2 to 4 μg/ml and dose-dependent rapid bactericidal activity against S. aureus. This activity was not influenced by resistance to other antistaphylococcal agents.     

Mitochondrial myopathies

The mitochondrial myopathies or encephalomyopathies with known biochemical defects can be divided into 5 groups: (1) defects of mitochondrial transport, such as CPT deficiency or carnitine deficiencies; (2) defects of substrate utilization, such as PDHC deficiency or defects of β-oxidation; (3) defects of the Krebs cycle, such as fumarase deficiency; (4) defects of oxidation-phosphorylation coupling, such as Luft disease, and (5) defects of the respiratory chain. These disorders are reviewed, with particular emphasis on the defects of the respiratory chain. Defects of complex I, III and IV show remarkable clinical and biochemical heterogeneity. All 3 complexes contain some subunits encoded by mtDNA and others encoded by nuclear DNA. At least some of the cytoplasmically made subunits appear to be tissue specific and may be developmentally regulated, thus explaining the genetic heterogeneity of these disorders.     

Effects of in utero antiretroviral exposure on mitochondrial DNA levels, mitochondrial function and oxidative stress

Objectives

HIV and antiretroviral (ART) exposure in utero may have deleterious effects on the infant, but uncertainty still exists. The objective of this study was to evaluate aspects of mitochondrial DNA (mtDNA) content, mitochondrial function and oxidative stress simultaneously in placenta, umbilical cord blood and infant blood in HIV/ART‐exposed infants compared with uninfected controls.

Methods

HIV‐1‐infected pregnant women and HIV‐1‐uninfected healthy pregnant controls were enrolled in the study prospectively. Placenta and umbilical cord blood were obtained at delivery and infant blood was obtained within 48 h of delivery. mtDNA content was determined for each specimen. Nuclear [subunit IV of cytochrome c‐oxidase (COX IV)]‐ and mitochondrial (COX II)‐encoded polypeptides of the oxidative phosphorylation enzyme cytochrome c‐oxidase were quantified in cord and infant blood. Placental mitochondria malondialdehyde (MDA) concentrations were measured as a marker of oxidative stress.

Results

Twenty HIV‐positive/HIV‐exposed and 26 control mother–infant pairs were enrolled in the study. All HIV‐infected women and their infants received ART. Placental MDA concentration and mtDNA content in placenta and cord blood were similar between groups. The cord blood COX II:IV ratio was lower in the HIV‐positive group than in the controls, whereas the infant peripheral blood mtDNA content was higher in the HIV‐exposed infants, but the infant peripheral blood COX II:IV ratio was similar. No infant had clinical evidence of mitochondrial disease or acquired HIV infection. In multivariable regression analyses, the significant findings in cord and infant blood were both most associated with HIV/ART exposure.

Conclusions

HIV‐exposed infants showed reduced umbilical cord blood mitochondrial enzyme expression with increased infant peripheral blood mitochondrial DNA levels, the latter possibly reflecting a compensatory mechanism to overcome HIV/ART‐associated mitochondrial toxicity.     

Assessment of endometrial volume by three-dimensional ultrasound prior to embryo transfer: clues to endometrial receptivity.

The aim of the present prospective study was to obtain quantitative data on endometrial volume by three-dimensional (3D) ultrasound at the time of embryo transfer in an in-vitro fertilization programme and to assess its value in predicting endometrial receptivity. The cycles (n = 72) were classified according to endometrial volume: group A <2 ml, group B 2-4 ml, and group C >4 ml. Comparisons of the groups showed that pregnancy and implantation rates were significantly lower (P < 0.05) in the group of patients with an endometrial volume <2 ml. Furthermore, no pregnancy was achieved with an endometrial volume <1 ml. It is concluded that endometrial volume by 3D transvaginal ultrasound may become a new objective parameter by which to predict endometrial receptivity.     

Hodgkin's disease: Correlation between causes of death at autopsy and clinical diagnosis

Purpose:The causes of mortality in Hodgkin's disease patients areinsufficiently known. Autopsy study is the fundamental procedure in theinvestigation of these causes. The present study analyzes the autopsiesperformed in a series of patients diagnosed as having Hodgkin's disease,determining the cause of death in each case and comparing the premortemclinical data and the postmortem findings.Patients and methods:A total of 486 patients diagnosed as havingHodgkin's disease between 1967 and 1996 were assessed. Autopsy was performedin 40 of the 144 deceased patients (28%). We reviewed the pathologicalfindings, effects of treatment, discordance between the clinical diagnosis andthe outcome of autopsy, and cause of death in each case.Results:The most common clinical causes of death in thosepatients with autopsy study were tumor progression (37%) and infections(43%) in those patients with autopsy study. The rate of discordancebetween the clinical and autopsy diagnoses in this study was 43%. Themost frequent location of residual Hodgkin's disease was in the lymph nodes.Conclusions:Autopsy study in Hodgkin's disease confirms a highrate of discrepancy between final clinical diagnosis and postmortem lesionsdespite advances in diagnostic methods. Autopsy revealed causes of deathdirectly related to the treatment, as well as some lesions directly relatedto patient death and secondary to treatment. Infectious processes are likelyto remain undetected and their symptoms can mimic tumor progression.     

Human hydatidosis in the central Andes of Peru: evolution of the disease over 3 years.

To document the natural history of Echinococcus granulosus infection and response to treatment of human hydatidosis, we reexamined 28 of 37 subjects with E. granulosus infection diagnosed in an epidemiological study conducted in 1994. Twenty-six (70%) of those 37 subjects underwent abdominal ultrasonography, chest radiography, and enzyme-linked immunoelectrotransfer blot assay in 1997. Medical records from two additional individuals were reviewed. Eight patients had their cysts surgically removed during the 3-year follow-up interval; no surgical complications or recurrences occurred. Among eight patients with cystic disease not treated by surgery, four had cyst-growth ranging from 0.4 to 1.4 cm during the 3-year interval. One patient developed a new cyst and another's simple cyst became septate; two developed new calcifications. Of 12 seropositive subjects with no cysts present in 1994, 10 reverted to seronegative, a finding that suggests a significant proportion of seropositive subjects in echinococcus-endemic regions may have only transient infection without disease. When cysts do develop, their growth rates and time courses are highly variable; over the 3-year period, we observed growth, septation, degeneration, and calcification of cysts.