Uranium from the environment enters the human body by ingestion with food and drink and by inhalation of respirable airborne uranium-containing dust particles or aerosols. Daily intake of uranium in food and water varies from approximately 1 to approximately 5 micrograms U/d daily in uncontaminated regions to 13-18 micrograms/d or more in uranium mining areas. A 70 kg, non-occupationally exposed 'Reference Man' living in Europe or in the United States has an estimated total body uranium content of about 22 micrograms. Uranium is absorbed from the intestine or the lungs, enters the bloodstream, and is rapidly deposited in the tissues, predominantly kidney and bone, or excreted in the urine. In the bloodstream, uranium is associated with red cells, and its clearance is relatively rapid. Renal toxicity is a major adverse effect of uranium, but the metal has toxic effects on the cardiovascular system, liver, muscle, and nervous system as well. Any possible direct risk of cancer or other chemical- or radiation-induced health detriments from uranium deposited in the human body is probably less than 0.005% in contrast to an expected indirect risk of 0.2% to 3% through inhaling the radioactive inert gas radon, which is produced by the decay of environmental uranium-238 in rocks and soil and is present in materials that are used to build dwellings and buildings where people live and work.

The primary mechanisms proposed for acetaminophen-induced hepatic necrosis should deplete protein thiols, either by covalent binding and thioether formation or by oxidative reactions such as S-thiolations. However, in previous studies we did not detect significant losses of protein thiol contents in response to administration of hepatotoxic doses of acetaminophen in vivo. In the present study we employed derivatization with the thiol-specific agent monobromobimane and separation of proteins by SDS-PAGE to investigate the possible loss of specific protein thiols during the course of acetaminophen-induced hepatic necrosis. Fasted adult male mice were given acetaminophen, and protein thiol status was examined subsequently in subcellular fractions isolated by differential centrifugation. No decreases in protein thiol contents were indicated, with the exception of a marked decrease in the fluorescent intensity, but not of protein content, as indicated by staining with Coomassie blue, of a single band of approximately 130 kDa in the mitochondrial fractions of acetaminophen-treated mice. This protein was identified by isolation and N-terminal sequence analysis as carbamyl phosphate synthetase-I (CPS-I) (EC 6.3.4.16). Hepatic CPS-I activities were decreased in mice given hepatotoxic doses of acetaminophen. In addition, hepatic glutamine synthetase activities were lower, and plasma ammonia levels were elevated in mice given hepatotoxic doses of acetaminophen. The observed hyperammonemia may contribute to the adverse effects of toxic doses of acetaminophen, and elucidation of the specific mechanisms responsible for the hyperammonemia may prove to be useful clinically. However, the preferential depletion of protein thiol content of a mitochondrial protein by chemically reactive metabolites generated in the endoplasmic reticulum presents a challenging and potentially informative mechanistic question.Acetaminophen is a widely used analgesic that appears to be safe when ingested in therapeutic doses, but causes marked hepatic damage in humans and experimental animals in larger doses (Mitchell et al., 1973a;Black, 1984). Although there appears to be general agreement that the mechanisms of cell damage by acetaminophen involve alterations of biological molecules by chemically reactive metabolites of the parent drug (Mitchell et al., 1973a), considerable disagreement persists regarding the relative contributions of different types of interactions (Nelson and Pearson, 1990). Alkylation or, somewhat more restrictively, arylation of hepatic proteins by a reactive metabolite(s) of acetaminophen was found to correlate with incidence and severity of injury (Jollow et al., 1973). It is reasonable to expect that the structure and/or functions of a protein would be affected adversely by the covalent attachment of a xenobiotic residue, but the question of the manner and extent to which covalent binding contributes to cellular injury has not been resolved (Smith et al., 1985a). Although covalent binding can occur in the absence of ...

ObjectiveStandard pre-operative assessment at our institution involves a comprehensive history and examination by a nurse practitioner. An electronic pre-operative assessment questionnaire, ePAQ-PO® (ePAQ, Sheffield, UK) has previously been developed and validated. This study aimed to determine the impact of ePAQ-PO on nurse consultation times and patient satisfaction in low-risk patients.MethodsThe duration of pre-operative assessment consultation was recorded for American Society of Anesthesiology physical classification 1 and 2 patients undergoing pre-operative assessment by an electronic questionnaire (ePAQ-PO group) and standard face-to-face assessment by a nurse practitioner (standard group). Patients were also asked to complete an eight-item satisfaction questionnaire. Eighty-six patients were included (43 in each group).ResultsAfter adjusting for the duration of physical examination, median (IQR [min-max]) consultation time was longer in the standard compared to the ePAQ-PO group (25 (18–33 [10–49]) min vs. 12 (8–17 [4–45]) min, respectively; p <0.001). Response rate for the satisfaction questionnaire was 93%. There was no significant difference in patient satisfaction scores (38/39 in standard group vs. 39/41 in ePAQ-PO group were fully satisfied with their pre-operative assessment; p = 0.494).ConclusionPre-operative assessment using ePAQ-PO is associated with a significant reduction of over 50% in the duration of the assessment without impacting on patient satisfaction.

The impact of in-utero isotretinoin exposure has been widely reported, with many affected pregnancies failing to reach term. Due to the low numbers of in-utero isotretinoin exposed pregnancies, the interactions between this drug and rare genetic defects such as microduplication 1q21.1 are unclear, particularly how they might manifest phenotypically. We present this case of in-utero isotretinoin exposure occurring in a child with microduplication 1q21.1. The child was born with congenital abnormalities which did not fit into a single syndrome. Regrettably in-utero exposure to isotretinoin continues to occur. We hope this case will trigger further discussion on the dangers of dispensing Isotretinoin without ensuring stringent pregnancy testing and its potential interaction with genetic abnormalities, in particular with microduplication 1q21.1.

S a r a h K . T a y lor a n d C h a r les V. S m it h D ep a r t m e n t of P e d ia t r ics, Ba ylor C olle ge of M ed icin e, H ou s t on , Te xa s , U S A R ece ived 25 Au g u s t 19 98 ; a cce p t ed 22 O ct ob e r 1 9 9 8 . T h is w or k w a s s u p p or t ed by G M 4 4 2 63 fr om t h e N a t ion a l I n s t it u t es of H e a lt h . Ad d r e s s cor r es p on d en ce t o D r. C h a r les V. S m it h , D e p a r t m en t of P e d ia t r ics, B a ylor C olle ge of M e d icin e, O n e B a y lor P la za , H ou s t on , Texa s 7 7 0 30 , U S A; e -m a il cs m it h @b cm .t m c.ed u Tox ic S u bs t a n ce M e ch a n is m s, 18 :67 ±8 2, 19 99 C op y r igh t