Lead contamination of surgical gloves by contact with a lead hand.

Background. "Lead hands" are frequently used to maintain hand and finger position in hand surgery. The malleability and strength of lead make it ideal for this purpose. The aim of this study was to determine the amount of lead transferred to a surgeon's glove during handling of a lead hand. Method. Sterile surgical gloves were wiped over the surface of a lead hand. The number of wipes was varied, the gloves were then sent to a trace elements laboratory, and the lead content transferred to each glove was determined. Results. The amount of lead transferred to each glove increased with increasing exposure to the lead hand. After twenty wipes, up to 2 mg of lead was transferred to the surgeon's glove. Covering the lead hand with a sterile drape markedly reduced the lead transferred to the surgeon's glove. Conclusion. Significant amount of lead is transferred on to the gloves after handling a lead hand. This risks wound contamination and a foreign body reaction. Covering the lead hand with a sterile drape may minimise the risk of surgical wound contamination.

A cancer research UK pharmacokinetic study of BPA-mannitol in patients with high grade glioma to optimise uptake parameters for clinical trials of BNCT.

This paper describes results to-date from a human pharmacokinetic study which began recruitment in December 2007. Results are presented for a single patient recruited in December 2007. A second patient was recruited in July 2008 but detailed data are not available at the time of writing. The trial is an open-label, non-comparative, non-therapeutic study of BPA-mannitol in patients with high-grade glioma, who will be undergoing stereotactic brain biopsy as part of the diagnostic process before definitive treatment. The study investigates the route of infusion (intra-venous (IV) or intra-carotid artery) and in each case will assess the effect of administration of mannitol as a blood-brain barrier disrupter. All cohorts will receive a 2 h infusion of BPA-mannitol, and for some cohorts an additional mannitol bolus will be administered at the beginning of this infusion. Measurements are made by inductively coupled plasma mass spectrometry (ICP-MS) of (10)B concentration in samples of blood, urine, extra-cellular fluid in normal brain (via a dialysis probe), brain tissue around tumour and tumour tissue. Additional analysis of the tumour tissue is performed using secondary ion mass spectrometry (SIMS). The first patient was part of the cohort having intra-venous infusion without mannitol bolus. No serious clinical problems were experienced and the assay results can be compared with available patient data from other BNCT centres. In particular we note that the peak (10)B concentration in blood was 28.1 mg/ml for a total BPA administration of 350 mg/kg which is very consistent with the previous experience with BPA-fructose reported by the Helsinki group.

Macromolecule oxidation and DNA repair in mussel (Mytilus edulis L.) gill following exposure to Cd and Cr(VI).

The oxidation of DNA and lipid was analysed in the marine mussel (Mytilus edulis) in response to exposure (10microg/l and 200microg/l) to cadmium (Cd) and chromium [Cr(VI)]. Concentration dependent uptake of both metals into mussel tissues was established and levels of gill ATP were not depleted at these exposure levels. DNA strand breakage in gill cells (analysed by the comet assay) was elevated by both metals, however, DNA oxidation [measured by DNA strand breakage induced by the DNA repair enzyme formamidopyrimidine glycosylase (FPG)] was not elevated. This was despite a statistically significant increase in both malondialdehyde and 4-hydroxynonenal - indicative of lipid peroxidation - following treatment with Cd. In contrast, both frank DNA stand breaks and FPG-induced DNA strand breaks (indicative of DNA oxidation) were increased following injection of mussels with sodium dichromate (10.4microgCr(VI)/mussel). The metals also showed differential inhibitory potential towards DNA repair enzyme activity with Cd exhibiting inhibition of DNA cutting activity towards an oligonucleotide containing 8-oxo-7,8-dihydro-2'-deoxyguanosine and Cr(VI) showing inhibition of such activity towards an oligonucleotide containing ethenoadenosine, both at 200microg/l. The metals thus show DNA damage activity in mussel gill with distinct mechanisms involving both direct and indirect (oxidative) DNA damage, as well as impairing different DNA repair capacities. A combination of these activities can contribute to adverse effects in these organisms.

Umbilical cord plasma concentrations of free morphine following single-dose diamorphine analgesia and their relationship to dose-delivery time interval, Apgar scores and neonatal respiration.

OBJECTIVE: To find the effect of dose-delivery interval on cord-blood levels of diamorphine metabolites and its effect on Apgar sores and neonatal respiration. STUDY DESIGN: Pilot study conducted in labour ward of a district general hospital. One hundred women who had normal delivery and received single dose of 7.5mg of intramuscular injection of diamorphine in labour were recruited in the study. A 2.0 ml sample of umbilical venous blood was collected from the placenta after delivery of the baby. The sample was analysed using RIA method to measure free morphine. Details about the labour and baby's condition at birth were recorded. RESULTS: The concentration of free morphine in the umbilical venous blood was significantly associated with the dose-delivery interval (coefficient (95% CI)=1.08(0.99-1.18), p<0.001). Twenty neonates had low Apgar score (< or =7) at 1 min. The odds of such a low score were raised with higher log free morphine in the cord venous plasma, but not statistically significantly (OR (95% CI)=5.3 (0.84-34), p=0.08). Fourteen neonates required resuscitation. The odds of requiring resuscitation were significantly raised with higher log free morphine: OR (95% CI)=9.3 (1.0-86), p=0.05. CONCLUSION: Concentration of free morphine in the umbilical venous blood after delivery was significantly associated with the dose-delivery interval and this had significant effect on the need for resuscitation.

Chromic acid burns: early aggressive excision is the best method to prevent systemic toxicity.

Chromium poisoning can occur from the cutaneous absorption of chromium from burns that are as small as 1% of the total body surface area. In this case report, we describe a patient with 10% total body surface area burns caused by hot chromic acid. The amount of chromium removed by peritoneal dialysis and the amount of chromium in the urine were estimated, as well as the chromium content in the excised skin, serum, and red blood cells. The extent of chromium load from this type of injury and subsequent risk of systemic poisoning is not predictable, and we therefore believe that systemic toxicity is best prevented by early excision of the burned skin.

Phase I trial of weekly scheduling and pharmacokinetics of titanocene dichloride in patients with advanced cancer.

PURPOSE: To determine the maximum-tolerated dose (MTD) and the dose-limiting toxicities (DLTs) of a weekly schedule of titanocene dichloride (TD) and to define the pharmacokinetics of titanium in plasma and urine. PATIENTS AND METHODS: Twenty patients with a median age of 58 years received 83 courses of TD. TD was given as 1-hour infusion at escalating doses from 70 to 185 mg/m2/wk. Pharmacokinetic analysis was performed in eight patients for total plasma titanium (TPTi) and in three patients for ultrafiltrable titanium (UFTi). RESULTS: At the fifth dose level (185 mg/m2/wk), a variety of DLTs were seen in five patients: fatigue in three, bilirubinemia in one, and hypokalemia in two. A further six patients were treated at 140 mg/m2; only one had dose-limiting creatinine elevation and this dose was therefore defined as the MTD. No myelosuppression or alopecia were observed. One patient with adenocarcinoma of unknown primary had a minor response. Pharmacokinetic analysis showed that TPTi maximum concentration (Cmax) values were linear with dose and elimination of TPTi was triphasic with a long terminal half-life (t1/2; median, 165 hours; range, 89 to 592). Between 7% and 24.3% of the total of administered titanium was eliminated in urine over the first 24 hours. In contrast, UFTi elimination was described by a one-compartment model with a t1/2 of 0.41 hours; peak levels of UFTi were 5.2% +/- 2.5% those of TPTi. CONCLUSION: The MTD of TD given on a weekly schedule is 140 mg/m2, with cumulative, but reversible creatinine and bilirubin elevation being the DLTs.

Serum copper and zinc concentrations in patients with burns in relation to burn surface area.

Serum zinc and copper concentrations were measured by flame atomic absorption spectroscopy in 34 patients between 1 and 3 weeks after thermal injury. Mean (range) admission burn surface area was 29.8% (10% to 79%), and mean (range) serum zinc and copper concentrations within the first postburn week were 0.59 (0.2 to 1.5) and 0.74 (0.1 to 1.6) mg/L, respectively. Serum copper concentration was inversely correlated with burn surface area (r = -0.611, p < 0.01), whereas serum zinc concentration showed no such association. In the first postburn week hypocupremia (< 0.7 mg/L) was found in 15 of 32 (48%) of patients and hypozincemia (< 0.7 mg/L) in 21 of 32 (68%). Serum copper concentrations in patients with less than 15% burns remained within normal limits throughout the study period, but hypozincemia was found in patients irrespective of burn surface area. Long-term monitoring of two patients with 79% and 70% burns showed initial hypocupremia and hypozincemia. Hypocupremia only resolved in the patient with 79% burns when skin healing was almost complete 75 days after burns. Postburn hypozincemia was found to be very variable and not associated with either serum albumin concentration or periods of clinical sepsis. Because major burn injuries are associated with hypocupremia, serial monitoring is recommended with appropriate copper supplementation.

Lead poisoning from Asian traditional remedies in the West Midlands--report of a series of five cases.

1. Traditional remedies are an unusual, but recognised cause of lead poisoning. Only two cases have previously been reported in this country. 2. We report a series of five cases of lead poisoning due to traditional remedies in the West Midlands. All developed typical clinical features. 3. Blood lead and zinc protoporphyrin (ZPP) concentrations were elevated 2-10 times the upper limit of normal. The remedies contained up to 60% lead by weight. One also contained traces of mercury, another arsenic, and a third aluminium and tin. 4. Confirmation of the medicines as the cause of the poisoning was made in one patient by measurement of lead isotopic ratios. 5. The present morbidity from traditional remedies may be far greater than is realised, and will continue until such time as the supply of harmful preparations can be effectively limited. There needs to be increased awareness of their dangers amongst doctors and the communities at risk. This will best be achieved by appropriately targeted education.

High-performance liquid chromatographic assay of plasma thalidomide: stabilization of specimens and determination of a tentative therapeutic range for chronic graft-versus-host disease.

Thalidomide is now widely used to treat chronic graft-versus-host disease, but its use is associated with non-teratogenic side effects such as peripheral neuropathy. To examine the value of monitoring plasma concentrations of the drug in such patients, we have developed a high-performance liquid chromatographic (HPLC) assay. The method uses 0.5 mL plasma, is linear to 10 mg/L and had a detection limit of 0.2 mg/L. Thalidomide in plasma specimens was unstable at physiological pH but could be stabilized for several weeks by simple acidification. We describe a protocol for monitoring patients treated with thalidomide which permits convenient transportation and storage of specimens and report, provisionally, that plasma concentrations in the range 1-7 mg/L are therapeutically effective in chronic graft-versus-host disease without adverse side effects.

Human papillomavirus type 1 E4 protein is a zinc-binding protein.

Study of the human papillomavirus (HPV) E4 gene product has focused largely on HPV type 1 (HPV 1) primarily because of the large quantities of protein that can be purified from HPV 1-induced warts. We have extended the characterization of the HPV 1 E4 protein and, in this study, have shown that protein purified from clinical material and a heterologous expression system contains the divalent metal ion zinc. Furthermore, using a [65Zn]Cl2 dot-blot assay, we have shown that this binding is specific for zinc and those divalent cations that are known to structurally substitute zinc in metalloproteins. Mutational analysis has demonstrated that histidine amino acids (residues 56, 86, and 121), but not the cysteine residue (115), are essential for the zinc-binding activity of the E4 protein. Two assayable functions of E4 are dimerization and the formation of E4/cytokeratin structures in cultured cells; however, neither activity is abrogated by the loss of zinc binding.

Simplified fluorometric assay of total selenium in plasma and urine.

We describe here a single-tube assay that may be applied to the whole range of selenium status in adult and pediatric patients, including depletion during parenteral or other nutrition. A specimen or aqueous standard, 100 microL, is digested with 0.5 mL of HNO3/HCIO4 (4/1 by vol, at 190 degrees C for 90 min), reduced with 0.5 mL of concentrated HCI (150 degrees C, 30 min), and complexed with 0.5 mL of 6.3 mmol/L 2,3-diaminonaphthalene (DAN) reagent in the presence of EDTA (60 degrees C, 30 min). The resulting fluorophore is extracted into cyclohexane and its fluorescence measured (excitation at 366 nm; emission at 544 nm). It is not necessary to control pH during the complexing step or to protect the DAN from light. The limit of detection of selenium is 10 micrograms/L (0.126 mumol/L); linearity of results extends to 2000 micrograms/L (25.3 mumol/L). Between-batch precision is 5%, analytical recovery 90%-96%. Performance is good as tested against Reference Materials and by participation in a National Quality Assurance Scheme.

Antenatal urinary screening for drugs of addiction: usefulness of sideroom testing?

Based on a pilot study of 400 samples at our Antenatal Clinic (which yielded 3.5% positives when assessed for amphetamines, cannabinoids and opiates) 600 consecutive patients attending Antenatal Booking Clinic had urine samples tested in the sideroom for amphetamines, barbiturates, cocaine metabolites, methadone and opiates using the Syva EMIT ETS apparatus. Positive samples were checked in the West Midlands Regional Laboratory for Toxicology, initially by EMIT-dau on a second ETS instrument and then by thin layer and gas chromatography. Two per cent produced a total of 14 positive EMIT results. Cocaine metabolites and methandone were not detected. Four specimens could not be confirmed as positive. In one sample, amphetamine-like compounds were isolated but not identified. Positive identification was made in the remaining seven specimens (two cannabinoid, two pseudoephedrine, one pseudoephedrine plus dihydrocodeine and two dihydrocodeine). There was a serious problem of false positive results observed in the initial sideroom testing. The value of sideroom testing for drugs of abuse was assessed in relation to the technical problems and to the small rate of drug positive samples.

Invasive carcinoma of the cervix in young women.

One hundred and seventy-six cases of cancer of the cervix in women age 35 years or less from 1959 to 1980 were compared with 65 cases occurring in the 5-year period from 1982 to 1986. The incidence of the disease in this age group changed little over this time, increasing from 9% to 11%. However, the incidence of adenocarcinoma cell types increased from 10% in the first period to 25% in the more recent cases. A change in management resulted in increased surgical emphasis in treatment; only 24% were treated surgically in the earlier group compared to 80% in the recent group. There has not been an increase in advanced cases or mortality in those young patients in recent years.

Strychnine poisoning: clinical and toxicological observations on a non-fatal case.

The successful supportive management of an acute strychnine ingestion is described; clinical and biochemical findings are reported. A gas chromatographic assay for serum strychnine has been applied to the analysis of 19 serial blood samples. Four hours post ingestion, the serum strychnine concentration was 1.6 mg/L. This declined with T 1/2 [corrected] of 10 hours over a period of 50 hours. First order kinetics are indicated. Management of strychnine poisoning in general is discussed in the light of this case and the limited knowledge of the pharmacokinetics of the alkaloid in man.

Indomethacin poisoning.

Two cases of indomethacin poisoning with supporting analytical data are described and the literature, which is limited to two reports, is reviewed. In overdose, indomethacin may produce the following non-life threatening symptoms: nausea, vomiting, abdominal pain, anorexia, drowsiness, headache, tinnitus, restlessness and agitation. The terminal elimination half-life in our two cases was respectively 6.8 hr and 2.9 hr which is similar to that found following a therapeutic dose.