Median nerve ultrasonography in distinguishing neuropathy sub-types: a pilot study.

BACKGROUND: The diagnostic potential of ultrasonography (US) in polyneuropathy has been studied rarely, with complex measurement/correction techniques. Whether US may be useful in clinical practice remains uncertain. MATERIALS AND METHODS: We aimed to ascertain the value of US, as performed routinely at our institution, in differentiating neuropathy sub-types. We prospectively studied 14 patients with chronic inflammatory demyelinating polyneuropathy (CIDP) and 14 patients with sensory axonal neuropathy (SAN). Median nerves were studied bilaterally at wrist and forearm by a radiologist blinded to the neuropathy sub-type. Nerve width (medial to lateral diameter), thickness (anterior to posterior diameter) and cross-sectional area were compared in between patient groups and anatomical sites. Optimal cut-off values were determined using receiver operating characteristic (ROC) curves. RESULTS: Largest measured median nerve thickness was significantly greater in patients with CIDP (P = 0.014), and ROC curve analysis indicated a cut-off offering a sensitivity of 57.1% for CIDP and specificity of 92.9% vs SAN. Nerves were wider and had larger cross-sectional areas, but were not thicker, at wrist compared to forearm in both patient groups. There was an equal prevalence in both patients with CIDP and SAN, of increased median nerve wrist-to-forearm area ratio, compatible with sub-clinical carpal tunnel syndrome. CONCLUSION: This prospective, blinded, pilot study is the first to indicate the diagnostic potential of US, as performed routinely, in distinguishing between acquired demyelinating and axonal neuropathy. These findings now require confirmation in larger, adequately designed studies, evaluating other nerves/nerve sites, assessing healthy controls and taking into account interrater and equipment variabilities.

Getting to the heel of the problem: plantar fascia lesions.

Heel pain is a frequent disabling symptom. Clinical diagnosis is often difficult with a large range of possible diagnoses. Lesions of the plantar fascia form an important group. We present a review describing the common lesions of the plantar fascia, including plantar fasciitis, plantar fascia rupture, plantar fibromatosis, and plantar xanthoma, and illustrate them with appropriate magnetic resonance imaging (MRI) and ultrasound imaging. We also address foreign-body reactions, enthesopathy, and diabetic fascial disease.

Acute ventricular and aortic thrombosis post chemotherapy.

We present a rare case of spontaneous arterial thrombosis in a 42-year-old male with an acute history of bilateral lower limb pain and weakness. The previous day he had received the first cycle of cisplatin-based chemotherapy for oesophageal adenocarcinoma (T2/3N0/M0). Computed tomography (CT) and angiography showed extensive abdominal aortic thrombus in a native non-aneurysmal or grossly atheromatous aorta with separate thrombus in the left ventricle. We suggest that poor left ventricular function, a hypercoaguable state secondary to malignancy and cisplatin based chemotherapy may have induced severe arterial and intra-cardiac thrombosis.

Reliable and reproducible LightCycler qPCR for HIV-1 DNA 2-LTR circles.

Highly active anti-retroviral therapy (HAART) has reduced the plasma load of HIV-1 to undetectable levels. It has however failed to eliminate the virus from other body compartments. Current methods for monitoring persistent viral replication in HIV-1+ patients require a large amount of blood and/or repeated tissue biopsies. Furthermore, some of the viral reservoirs, such as brain and eye, are inaccessible for sampling. The detection of episomal HIV-1 DNA 2-LTR circles in CD4+ cells is indicative of recent, acute infection events. This paper describes a reliable and reproducible LightCycler-based assay for the quantitative measurement of HIV-1 DNA 2-LTR circles in human peripheral blood mononuclear (PBMN) cells. It details the modifications to the DNA extraction procedure and to the LightCycler PCR procedure that were required to achieve this. This new surrogate marker of persistent viral replication can now be reliably, reproducibly and robustly used to study the clinical progress of large numbers of patients whose plasma HIV-1 RNA has been reduced to undetectable levels by anti-retroviral drugs.

LightCycler qPCR optimisation for low copy number target DNA.

The LightCycler is a rapid air-heated thermal cycler which incorporates a fluorimeter for the detection and quantification of Polymerase Chain Reaction (PCR) amplified products. It provides real-time cycle-by-cycle analysis of product generation. Amplification occurs in glass capillary tubes. The products are detected using a fluorescent double stranded DNA binding dye or fluorescent probes. However, conditions that work well in conventional PCR reactions do not readily translate to the LightCycler. Whilst using this new technology to study an infectious pathogen in human tissue samples, several parameters were identified which can have an adverse effect on the reliable and reproducible quantification of low copy number target DNA. They included abstraction of PCR reagents on glass, primer-dimer formation, non-specific product generation, and a failure to amplify low copy number target when it is present in a high background of human chromosomal DNA. For each problem identified, several solutions are described. Novel approaches are also described to ensure that amplification of target DNA and of the quantification standards occurs with the same efficiency. With appropriate changes to the protocols currently in use, LightCycler quantitative Polymerase Chain Reaction (LC-qPCR) can be used to achieve a level of accuracy that exceeds that of an enzyme immunoassay. The LC-qPCR optimisation strategies described are of particular relevance when applying this technology to the study of pathogens in tissue samples. The technique offers the enormous potential for reliable and reproducible quantitative PCR of low copy number target DNA.

The paradox of improved antiretroviral therapy in HIV: potential for nutritional modulation?

Chronic infection with HIV type 1 is associated with alterations in macronutrient metabolism, specifically elevated plasma lipids, glucose and reduced insulin sensitivity. These alterations are most severe in patients at the later stages of AIDS, indicating a relationship with disease progression. Recently, a metabolic syndrome, termed lipodystrophy, has been described in successfully-treated HIV patients in whom the altered macronutrient metabolism of HIV infection appears to be amplified markedly, with concurrent alterations in adipose tissue patterning. This syndrome presents a paradox, as before the development of highly-active antiretroviral therapy (HAART) the most severe perturbations in metabolism were observed in the sickest patients. Now, the patients that respond well to therapy are showing metabolic perturbations much greater than those seen before. The implications of this syndrome are that, whilst life expectancy may be increased by reducing viral load, there are concomitant increases in the risk of cardiovascular disease, diabetes and pancreatitis within this patient population. The aetiology of the syndrome remains unclear. In a collaborative trial with the Chelsea and Westminster Hospital in London we have used stable-isotope-labelled fatty acids to examine the hypothesis that treatment with HAART causes a delayed clearance of dietary lipid from the circulation, resulting in the retention of lipid within plasma and the downstream changes in insulin and glucose homeostasis. This hypothesis would indicate a role for low-fat diets, exercise and drugs that reduce plasma lipid or insulin resistance, in modulating the response to antiretroviral therapy in HIV infection.

In vivo rates of erythrocyte glutathione synthesis in children with severe protein-energy malnutrition.

Although the compromised GSH status of children with edematous protein-energy malnutrition (PEM) has been documented, the in vivo kinetic mechanism(s) responsible for this is not known. To determine if decreased synthesis contributes to the alteration of GSH homeostasis, the fractional and absolute rates of synthesis of erythrocyte GSH were determined shortly after admission (study 1), approximately 9 days postadmission (study 2), and at recovery (study 3) in seven children with edematous PEM and seven children with nonedematous PEM. Children with edematous PEM had significantly lower erythrocyte GSH and slower absolute rates of GSH synthesis than children with nonedematous PEM both shortly after admission, when they were both malnourished and infected, and approximately 9 days later, when the infection had resolved but they were still malnourished. At these times, the edematous group also had significantly lower erythrocyte GSH concentrations and absolute rates of synthesis than at recovery. Plasma and erythrocyte-free cysteine concentrations of the edematous group were significantly lower at studies 1 and 2 than at recovery. In contrast, erythrocyte GSH concentrations, rates of GSH synthesis, and plasma and erythrocyte free cysteine concentrations of the nonedematous group were similar at all three time points and greater at studies 1 and 2 than in the edematous group. These results confirm that GSH deficiency is characteristic of edematous PEM and suggest that this is due to a reduced rate of synthesis secondary to a shortage in cysteine.

Diagnosis and management of male breast enlargement in patients with HIV/AIDS.

There have been several recent reports describing gynecomastia in HIV-1-seropositive patients treated with HAART. However, the etiology of gynecomastia in this setting is far from clear. In this article, we describe the main issues in diagnosis and treatment of gynecomastia and stress the importance of differentiating between "true" gynecomastia and "lipomastia" (pseudogynecomastia), characterized by subcutaneous fat deposition. The importance of switching antiretroviral drugs is also discussed. In addition, newer medical therapies are highlighted.

Acute-phase protein response to infection in severe malnutrition.

It is not known whether malnourished infants can mount a comprehensive acute-phase protein (APP) response and, if so, whether this is achieved by increasing APP synthesis rates. To address these issues, we measured 1) the plasma concentrations of five APPs (C-reactive protein, alpha1-acid glycoprotein, alpha1-antitrypsin, haptoglobin, and fibrinogen) and 2) the synthesis rates of three APPs (alpha1-antitrypsin, haptoglobin, and fibrinogen) using a constant intragastric infusion of [2H3]leucine in nine infected marasmic children at approximately 2 days postadmission (study 1), approximately 9 days postadmission when infections had cleared (study 2), and approximately 59 days postadmission at recovery (study 3). Except for fibrinogen, the plasma concentrations of all APPs were higher in study 1 than in studies 2 and 3. Although the rate of synthesis of haptoglobin was significantly greater in study 1 than study 2, the rates of fibrinogen and alpha1-antitrypsin synthesis were similar in all three studies. These results show that 1) severely malnourished children can mount an APP response to infection which does not include fibrinogen and 2) the APP response is accomplished through different mechanisms.

Repletion of the plasma pool of nutrient transport proteins occurs at different rates during the nutritional rehabilitation of severely malnourished children.

Increased morbidity and mortality are associated with lower plasma protein concentrations in children with severe protein-energy malnutrition. However, the kinetic changes responsible for repletion of the plasma pools of nutrient transport proteins and the rapidity of their replenishment in these children have not been determined. This study was undertaken to determine whether an increased rate of synthesis is the mechanism responsible for repletion of the plasma retinol-binding protein, transthyretin and high density lipoprotein-apolipoprotein A1 concentrations of children with severe malnutrition during nutritional rehabilitation. The plasma concentrations and synthesis rates of retinol-binding protein, transthyretin and high density lipoprotein-apolipoprotein A1 were measured using a constant intragastric infusion of 2H3-leucine in 22 children with severe protein-energy malnutrition, at approximately 2 d postadmission (study 1), approximately 8 d post-admission when infections were under control (study 2) and approximately 59 d postadmission at recovery (study 3). In study 1 the plasma concentrations and rates of synthesis of all the proteins were lower compared with values at recovery. In study 2, retinol-binding protein and transthyretin concentrations and absolute synthesis rates increased to the recovered values seen in study 3, but the high density lipoprotein-apolipoprotein A1 concentration and synthesis rate remained significantly lower. These results suggest that repletion of the plasma pool of these three nutrient transport proteins occurs at different rates, through an increase in the rate of synthesis.

Transferrin kinetics are altered in children with severe protein-energy malnutrition.

This study was undertaken to determine the following: 1) the kinetic changes responsible for the depletion and repletion of plasma transferrin (Tr) concentration in children with protein-energy malnutrition (PEM); 2) the role of infection in mediating these changes; and 3) whether plasma Tr concentration is related to body protein status. We measured plasma Tr concentration, and fractional (FSR) and absolute (ASR) Tr synthesis rates with the use of a constant intragastric infusion of 2H3-leucine in 14 children with PEM, at 2 d postadmission (study 1), 8 d postadmission when infections were under control (study 2), and at recovery (study 3). In studies 1 and 2, the children synthesized less Tr and had lower Tr concentrations compared with values at recovery. When infections were controlled, plasma Tr concentration rose, but Tr synthesis was unchanged. There were only fair correlations (P < 0. 05) between plasma Tr concentrations and indices of wasting. Concerning malnourished children, we reached the following conclusions: 1) changes in the Tr pool size are achieved mainly through changes in synthesis rate; 2) infections play a minor role in reducing the Tr pool through either changes in the rate of catabolism or loss from the intravascular space; and 3) Tr concentration is not a very good indicator of protein nutritional status.

Albumin kinetics in edematous and nonedematous protein-energy malnourished children.

The kinetic changes responsible for decreased plasma albumin and the relation between plasma albumin and the edema of protein-energy malnutrition (PEM) were investigated by measuring the plasma concentration, fractional (FSR) and intravascular absolute (ASR) synthesis rates of albumin in seven edematous and seven nonedematous children with PEM by using constant intragastric infusions of [2H3]leucine. Studies were done 2 d postadmission (study 1), 8 d postadmission (study 2), and at recovery (study 3). In study 1 there were no significant differences in plasma albumin concentrations in nonedematous and edematous children. In both groups, albumin concentrations but not FSRs were lower in studies 1 and 2 than in study 3. The ASR was lower only in edematous patients. These results suggest that repletion of the albumin pool of children with PEM is not mediated by changes in the FSR, and the edema of malnutrition is not solely due to hypoalbuminemia.

Evidence for decidua-trophoblast interactions in early human pregnancy.

Medium conditioned by decidual cells decreased the growth of cultured BeWo choriocarcinoma cells. The degree of inhibition was dependent on the concentration of the conditioned medium used, and suggested that maternal decidua might regulate the growth of the fetal placenta. Medium from BeWo cells and primary trophoblast had the opposing effect and increased the growth of cultured decidual cells for up to 120 h of culture. These results suggest that a regulatory loop to control placental and decidual growth exists at the materno-fetal interface, and this may be an important factor in the development of adequate placentation and the subsequent growth of the placenta during pregnancy.