'SHOwing' the way.
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Attitude of Health Personnel↗
Biomedical subjects
Jan Smith
Publications and source records attributed to Jan Smith.
The role of physiotherapy in weight control.
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Exercise Therapy↗
Effect of the militarily-relevant heavy metals, depleted uranium and heavy metal tungsten-alloy on gene expression in human liver carcinoma cells (HepG2).
Depleted uranium (DU) and heavy-metal tungsten alloys (HMTAs) are dense heavy-metals used primarily in military applications. Chemically similar to natural uranium, but depleted of the higher activity 235U and 234U isotopes, DU is a low specific activity, high-density heavy metal. In contrast, the non-radioactive HMTAs are composed of a mixture of tungsten (91-93%), nickel (3-5%), and cobalt (2-4%) particles. The use of DU and HMTAs in military munitions could result in their internalization in humans. Limited data exist however, regarding the long-term health effects of internalized DU and HMTAs in humans. Both DU and HMTAs possess a tumorigenic transforming potential and are genotoxic and mutagenic in vitro. Using insoluble DU-UO2 and a reconstituted mixture of tungsten, nickel, cobalt (rWNiCo), we tested their ability to induce stress genes in thirteen different recombinant cell lines generated from human liver carcinoma cells (HepG2). The commercially available CAT-Tox (L) cellular assay consists of a panel of cell lines stably transfected with reporter genes consisting of a coding sequence for chloramphenicol acetyl transferase (CAT) under transcriptional control by mammalian stress gene regulatory sequences. DU, (5-50 microg/ml) produced a complex profile of activity demonstrating significant dose-dependent induction of the hMTIIA FOS, p53RE, Gadd153, Gadd45, NFkappaBRE, CRE, HSP70, RARE, and GRP78 promoters. The rWNiCo mixture (5-50 microg/ml) showed dose-related induction of the GSTYA, hMTIIA, p53RE, FOS, NFkappaBRE, HSP70, and CRE promoters. An examination of the pure metals, tungsten (W), nickel (Ni), and cobalt (Co), comprising the rWNiCo mixture, demonstrated that each metal exhibited a similar pattern of gene induction, but at a significantly decreased magnitude than that of the rWNiCo mixture. These data showed a synergistic activation of gene expression by the metals in the rWNiCo mixture. Our data show for the first time that DU and rWNiCo can activate gene expression through several signal transduction pathways that may be involved in the toxicity and tumorigenicity of both DU and HMTAs.
Carcinoma, Hepatocellular↗
Noncardiogenic pulmonary edema induced by a molecular adsorbent recirculating system: case report.
Noncardiogenic pulmonary edema is a well-recognized manifestation of acute lung injury which has been related, among others, to blood or blood-product transfusion, intravenous contrast injection, air embolism, and drug ingestion. We describe two cases of noncardiogenic pulmonary edema after use of a molecular adsorbent recirculating system, a cell-free dialysis technique. Patients in this series presented at our institution to be evaluated for liver transplantation. Subsequently, they developed an indication for the molecular adsorbent recirculating system. Two patients of 30 (6.6%) treated with the molecular adsorbent recirculating system for acute-on-chronic liver failure and intractable pruritus had normal chest X-rays before treatment and developed severe pulmonary edema, in the absence of cardiogenic causes, following use of the molecular adsorbent recirculating system. For each patient we reviewed the history of blood or blood-product transfusion, echocardiograms if available, daily chest X-rays, and when available pre- and postmolecular adsorbent recirculating systemic blood pressure, central venous pressure, pulmonary arterial pressures, cardiac output, cardiac index, systemic vascular resistance index, and arterial blood gas. Our data suggest that the molecular adsorbent recirculating system may cause noncardiogenic pulmonary edema, possibly by an immune-mediated mechanism.
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Effect of molecular adsorbent recirculating system in hepatitis C virus-related intractable pruritus.
Intractable pruritus is more common in cholestatic liver diseases and may be the presenting symptom and/or major complaint of hepatitis C and/or hepatitic C virus-related cirrhosis. From September 2000 to May 2002, three patients affected by intractable pruritus secondary to hepatitis C cirrhosis that failed medical treatment were treated with a molecular adsorbent recirculating system (MARS). MARS is an artificial liver support system that aims to clear the blood of metabolic waste products normally metabolized by the liver. Each patient underwent seven MARS sessions. Liver function tests, the 36-Item Short Form quality-of-life test, visual analog scale for itching, and bile acid measurement in the serum, albumin circuit and ultrafiltrate were performed before and after each MARS session. Moreover, at hospital admission, each patient underwent a psychological workup and abdominal imaging study. Subjective improvement in pruritus and quality of life, along with a decrease in serum bile acid concentration, was observed in every patient; no patient underwent retreatment and/or liver transplantation up to a 9-month follow-up. One patient died 201 days after MARS treatment. Although we observed a decreased level of serum bile acids, one cannot conclude that this was the mechanism of action for the reduction in pruritus intensity in patients in our series. Different toxins and/or a placebo effect might have had a role in this setting.
Aged↗