Search

Background: This report describes a large international chocolate-associated Salmonella outbreak originating from Germany., Methods: We conducted epidemiologic investigations including a case-control study, and food safety investigations. Salmonella (S.) Oranienburg isolates were subtyped by the use of pulsed-field gel electrophoresis (PFGE)., Results: From 1 October 2001 through 24 March 2002, an estimated excess of 439 S. Oranienburg notifications was registered in Germany. Simultaneously, an increase in S. Oranienburg infections was noted in other European countries in the Enter-net surveillance network. In a multistate matched case-control study in Germany, daily consumption of chocolate (matched odds ratio [MOR]: 4.8; 95% confidence interval [CI]: 1.3-26.5), having shopped at a large chain of discount grocery stores (MOR: 4.2; CI: 1.2-23.0), and consumption of chocolate purchased there (MOR: 5.0; CI: 1.1-47.0) were associated with illness. Subsequently, two brands from the same company, one exclusively produced for that chain, tested positive for S. Oranienburg. In two other European countries and in Canada chocolate from company A was ascertained that also contained S. Oranienburg. Isolates from humans and from chocolates had indistinguishable PFGE profiles. No source or point of contamination was identified. Epidemiological identification of chocolate as a vehicle of infections required two months, and was facilitated by proxy measures., Conclusions: Despite the use of improved production technologies, the chocolate industry continues to carry a small risk of manufacturing Salmonella-containing products. Particularly in diffuse outbreak-settings, clear associations with surrogates of exposure should suffice to trigger public health action. Networks such as Enter-net have become invaluable for facilitating rapid and appropriate management of international outbreaks.

Background: National recommendations for vaccine policies in Germany were changed in 2001. Following this advice childhood vaccination for nine preventable diseases including measles, mumps, and rubella (MMR) should be completed within the first two years of life. To achieve this it is recommended that plurivalent combination vaccines should be used. As data on current practice is generally rare and not available for the State of Hamburg, a cross-sectional study amongst families from Hamburg with children born during the year 2000 was conducted between April and August 2003., Methods: A random sample from the resident register was drawn. Structured telephone interviews were conducted. Information on vaccine status and time of vaccination was collected based on individual vaccination documents., Results: 366 families were included in the study. 286 families (78 %) provided information. For 223 families the statements were reliably confirmed. In this group 180 children (80.7 % CI 76 - 86 %) had received at least one dose of MMR vaccine. 112 (50.2 % CI 44 - 57 %) had received two doses. Within the recommended time intervals 49 % had received the first, respectively 46 % had received the second MMR vaccination. A hexavalent contains vaccine containing the other six antigens was used for 138 of the 223 children (62 % CI 55 - 68 %). For 84 of those children (61 %) vaccination was completed with four doses. For 73 children other combinations including single valent vaccines were used. Among those for only 20 children (27.3 %) a completed vaccination status was reached during the recommended time interval. This gap was mainly due to missing hepatitis B vaccinations. The chance for their vaccination to be completed was more than twice as high for children who received the hexavalent combination vaccine compared to the others (RR 2.5; 95 % CI 1.6 - 3.9)., Discussion: The results indicate that the recommendations to complete MMR vaccinations earlier are recognised. Nevertheless about half of the children were vaccinated later than recommended. In order to achieve vaccination coverage which will allow to achieve the goal of measles eradication substantial efforts are still required. Due to relatively large rates of incomplete vaccinations for the other antigens activities should focus on a timely completion of the gaps. The potential of combination vaccines to reach this aim is evident.

A pandemic appearance of influenza A virus must be expected at any time. The limitations of health preserving and life-saving resources, which will inevitably be reached in the event of a pandemic, will be accompanied by ethical and possibly social conflicts, which can be lessened or resolved only through precautionary planning, clearly specified competencies and transparent decisions within a social consensus. In case of a shortage of vaccines and virostatic agents, decisions will have to be made with regard to the segment of the population that absolutely must be vaccinated. It is currently estimated that a (monovalent) vaccine developed for a new pandemic strain would only suffice for the single vaccination of approximately half of the German population after a year; only 10-14 million vaccine dosages would be available to provide basic immunization and single boosters to personnel required to maintain basic medical care and essential infrastructure after half a year. In the event of local influenza outbreaks, antiviral chemotherapeutic agents could be used to close the gap until a vaccine can become effective. Even if suitable influenza vaccines and virostatic agents are not sufficiently available at the start of a pandemic, it is still possible to at least prevent an outbreak of two of the most feared secondary infections that accompany influenza: pneumococcal pneumonia or meningitis and illnesses resulting from Haemophilus influenzae. Agreement still needs to be reached with manufacturers for guaranteeing the necessary vaccine production or ensuring that they have a sufficient stock to meet the minimum demand for antiviral agents and agents for symptomatic treatment.

The following conceptual framework formed the basis for a common decision made by the health ministers of Germany's 16 federal states to set up an influenza pandemic preparedness plan. The worst case scenario was used, on the basis of the data from the pandemic of 'Spanish flu', in 1918-20. The priority groups for vaccination were assessed, as well as the potentially available antiviral treatments. National policies could be highly improved by a common European view.

Necessary anti-epidemic measures have to be promulgated or taken immediately in case of a suspected case of pneumonic plague or a viral haemorrhagic fever which can be transmitted from human to human. A live threatening highly contagious infectious disease may occur at any place in Germany. Therefore each health office should have the relevant information on the available infrastructure in Germany concerning treatment and competence centres, diagnostic laboratories, dispatch of samples and patient transportation. They should also be able to give qualified recommendations to physicians and hospitals concerning the necessary measures in such a case. Contacts at risk have to be notified. Based on a risk assessment and the special living conditions of the contact person they should decide if and which further measures have to be initiated, especially in the case of post-exposure prophylaxis, separation and prohibition of work. In general, imported cases of dangerous infectious diseases quickly find the interest of the media, including all the implications resulting from this. A well-organized cooperation with the media and public relations helps to avoid unnecessary irritations and panic.

One hundred fifty patients undergoing carotid endarterectomy were randomly assigned to receive intravenous 10% dextran 40 or placebo. Transcranial Doppler monitoring of the ipsilateral middle cerebral artery 0 to 1 hour postoperatively detected embolic signals in 57% of placebo and 42% of dextran patients, with overall embolic signal counts 46% less for dextran (p = 0.052). Two to 3 hours postoperatively, embolic signals were present in 45% of placebo and 27% of dextran patients, with embolic signal counts 64% less for dextran (p = 0.040). We conclude that dextran reduces embolic signals within 3 hours of CEA.

Wilson's disease, the most common inherited disorder of copper metabolism, is a recessive genetic condition. The clinical presentation of Wilson's disease is very variable. It is characterised by low serum copper and caeruloplasmin concentrations coupled with the pathological accumulation of copper in the tissues. However, there are diagnostic difficulties and these are discussed. The current value of DNA diagnosis, both in gene tracking in families or as applied to de novo cases, is examined. Wilson's disease can be treated successfully but treatment must be life long. Patients are best treated by specialist centres with experience and expertise in the condition.

In June 1998, an increased number of persons with Salmonella blockley infection were reported from one German state. Because S. blockley is extremely uncommon in Germany, a case-control study was performed in order to find the source. A total of 13 patients met the case definition. Nine of 12 cases and 2 of 21 controls with food consumption histories reported eating smoked eel (OR 28.5; 95% CI 3.9-235.3). The consumed eel came from four different local smokeries, but could be traced back to fish farms in Italy. This outbreak indicates that eel may be a vehicle for salmonella infection and that the smoking process may not eliminate bacterial contamination from raw fish.

In the week following a carnival during 19-24 February 1998, an outbreak of meningococcal disease occurred in a rural German county. The available isolates belonged to phenotype C:2a:P1.2,5 and were clonally related by pulsed-field gel electrophoresis. A case-control study was done to identify risk factors for the outbreak and to define possible vaccination target groups. Five persons aged 13-16 years who fell ill during 24-27 February were included in the study. Four of 5 cases and 10 of 32 controls visited local discotheques (OR = 8.8; P = 0.06). Cases also visited discotheques more frequently than controls (chi2 for trend, P = 0.0002). Multiple discotheques during the carnival may have been predominant locations of transmission in this outbreak. Because this risk factor was limited in time, a mass community vaccination campaign was not initiated.

One hundred and fifty-seven liver samples from newborns and infants who had died from sudden infant death syndrome (SIDS) or other known causes have been analysed by ICP-MS for Ag, Cd, Co, Pb and Sb. The median concentrations found were: 15.4 (Ag), 2.9 (Cd), 15.9 (Co), 65.2 (Pb) and 1.8 (Sb) ng g-1 wet mass. There was no measurable difference in the concentrations of any of these elements between the SIDS and non-SIDS groups. The validity of the results was assessed by analysis of appropriate reference materials, interlaboratory comparison and isotope dilution analysis. The instrumental limits of detection were 0.25 (Ag), 0.14 (Cd), 0.21 (Co), 3.8 (Pb) and 0.38 (Sb) ng g-1 wet mass. The limits of detection of the method depend on the reagent blank and the extent of background contamination.

Almost 2700 samples of human renal cortex have been collected from throughout the UK over a 16 year period from 1978 to 1993. The mean Cd concentration was 19 micrograms g-1 and the median 16 micrograms g-1. Smokers were, on average, about 5 micrograms g-1 higher than non-smokers. Cd increased from low concentration in the young to a maximum of 23 micrograms g-1 in middle age followed by a decrease in old age. Subjects who had died of renal disease had lower Cd concentrations. Geographical variations in the UK are small and the concentrations appear to be static over the 16 year period. Some 3.9% of the population had Cd concentrations > 50 micrograms g-1, the critical level at which beta 2-microglobulin appears in urine.

Laboratory methods for the measurement of micronutrients are usually based upon determinations in the peripheral blood. Most are relatively insensitive, but can screen for impending acute deficiency or toxicity. The metabolic responses to disease, injury and infection may alter the laboratory findings independently of dietary supply. Methods based upon the intra-cellular biochemical function of individual micronutrients are becoming available and can detect more marginal deficiencies. The investigation of general populations for micronutrient depletions largely relies upon clinical and epidemiological evaluation of responses to controlled trials of supplementation.

This study examined the effect of an inflammatory response on measures of antioxidant status in patients with non-small cell lung cancer (NSCLC). In healthy, control subjects (n = 13) and NSCLC patients (n = 22) fasting concentrations of albumin, C-reactive protein, cholesterol, and the antioxidants alpha-tocopherol, retinol, lutein, lycopene, and alpha- and beta-carotene were measured. The two groups were similar in terms of age, sex, and body mass index. However, the cancer group had an inflammatory response as evidenced by significantly increased C-reactive protein concentrations. Concentrations of all the measured antioxidants of the NSCLC group were significantly lower than those of the control group (P < 0.01). The lowest concentrations were those of the carotenoids lycopene and alpha- and beta-carotene. In the cancer group there were significant negative correlations between concentrations of C-reactive protein and retinol (r = -0.682, P < 0.01), alpha-tocopherol (r = -0.464, P < 0.05), and lutein (r = -0.599, P < 0.01). The results of this study have implications for the interpretation of circulating antioxidant concentrations in patients with NSCLC.

Methods are presented for the determination by ICP-MS of antimony in body fluids and tissues of infants. Urine, serum and whole blood specimens are prepared for analysis by simply diluting 200 microliters sample volumes (1 + 14) with water and adding indium as internal standard. Liver and lung tissues are digested using 16 M HNO3 either in open quartz vessels at 150 degrees C or in sealed vessels with microwave heating. The acid digests are diluted with water and indium is added as internal standard for ICP-MS measurements. All analyses were subjected to stringent internal quality control protocols. Accuracy was assessed by recoveries, repeated analyses and by analysis of NIST SRMs 1577a Bovine Liver and 1566a Oyster Tissue. Precisions of analyses were better than 5-10% in the ranges 0.1-0.3 microgram l-1 for urine, serum and blood; and at 7-25 ng g-1 in tissues. Detection limits were 0.7 ng g-1 in liver, 0.8 ng g-1 in lung, and 0.01 microgram l-1 in urine, serum and blood. The need to employ validated procedures for specimen collection and to give considerable attention to pre-analytical factors in order to avoid adventitious contamination with antimony is demonstrated.

Objectives: Perioperative ischaemic stroke is the leading cause of morbidity and mortality associated with carotid endarterectomy (CEA). The aim was to test the hypotheses that the detection of microembolic ultrasonic signals (MES) with transcranial Doppler ultrasound (TCD) during and after the operation may be of value in identifying patients at increased perioperative stroke risk., Design: Open prospective case series., Patients and Methods: Eighty-one consecutive patients undergoing CEA with TCD monitoring. Preoperative, intraoperative and interval postoperative TCD monitoring of the middle cerebral artery (MCA) ipsilateral to the operated carotid artery. On-line pre- and intraoperative MES counting and blinded off-line analysis of postoperative MES counts. End-points were any focal neurological deficit and death at 30 days postoperatively., Results: MES were detected in 94% of patients intraoperatively and 71% of cases during the first postoperative hour. MES counts ranged from 0 to 25 per operative phase (range of median counts 0-8) and from 0 to 212 per hour postoperatively (range of median counts 0-4). Eight cases (10%) developed postoperative MES counts greater than 50/h. Five of these eight cases evolved ischaemic neurological deficits in the territory of the insonated MCA, indicating a strong association between frequent postoperative microembolism and the development of early cerebral ischaemia (chi 2 = 34.2, p < 0.0001). Intraoperative MES were not associated with clinical outcome measures., Conclusions: MES counts of greater than 50/h in the early postoperative phase of carotid endarterectomy are predictive of the development of ipsilateral focal cerebral ischaemia.

We report the results of the first complete study of nickel metabolism in human subjects using a stable nickel isotope (62Ni) as tracer. Four healthy adult subjects (two women and two men) fasted overnight before ingesting 10 microg 62Ni/kg body wt. Blood samples were drawn after fixed intervals of time and the total daily output of urine and feces was collected for the first 5 d after dose ingestion. 62Ni in plasma, urine, and feces was determined by isotope-dilution inductively coupled plasma-mass spectrometry with 61Ni. The direct measurement of the fecal excretion of the tracer allowed a reliable assessment of nickel absorption from the gastrointestinal tract and we found no evidence of the excretion of absorbed nickel via the gut. The percentage absorption calculated from the amount of 62Ni excreted in the feces ranged from 29% to 40%. Urinary excretion over 5 d ranged from 51% to 82% of the absorbed dose. Plasma 62Ni peaked between 1.5 and 2.5 h after ingestion and decreased by a factor of > 10 over the next few days. We observed low between-subject variability of nickel absorption and excretion. Confounding factors such as contamination and dietary intake of nickel, which hampered earlier measurements in subjects dosed with naturally abundant nickel, were eliminated by using the tracer isotope 62Ni.

Cerebral ischaemia, the most frequent serious complication of carotid endarterectomy (CEA), usually occurs in the early postoperative period and is often the result of thromboembolism. We hypothesized that the early postoperative detection of microembolic ultrasonic signals (MES) with transcranial Doppler ultrasound (TCD) may be of value in identifying patients at risk of postoperative cerebral ischaemia and that the MES rate may be an important determinant in risk prediction. Sixty-five patients undergoing CEA were studied at intervals up to 24 h postoperatively with TCD insonation of the middle cerebral artery ipsilateral to the operation side. Study design was open and prospective with blinded off-line analysis of MES counts. End-points were any focal ischaemic neurological deficit and/or death up to 30 days postoperatively. MES were detected in 69% of cases during the first hour postoperatively with counts ranging from 0 to 212 MES/h (means 19 MES/h; SEM +2- 4.5; median 4 MES/h). In seven cases (10.8%) counts were > 50 MES/h. Five of these seven cases developed ischaemic neurological deficits in the territory of the insonated middle cerebral artery during the monitoring period. The positive predictive value of counts > 50 MES/h for cerebral ischaemia was 0.71. Frequent signals (> 50 MES/h) occur in approximately 10% of cases in the early postoperative phase of CEA and are predictive for the development of ipsilateral focal cerebral ischaemia.

To assess body magnesium status in various illness states in older people by measurement of serum magnesium (S Mg) and erythrocyte magnesium (E Mg) and to explore the limitations of E Mg measurement. S Mg and E Mg were measured in 150 consecutive out-patients, mean age 77 years, and in 100 consecutive in-patient admissions, mean age 80 years. Results were analysed for different diagnostic groups S Mg was normally distributed for both in-patients and out-patients, mean values 0.79 mmol/l and 0.77 mmol/l respectively. In-patient E Mg concentrations were often higher but the distribution was considerably skewed, median 2.28 mmol/l, mean 2.35 mmol/l. Out-patient E Mg concentration followed a near normal distribution, median 2.32 mmol/l, mean 2.30 mmol/l. There was a significant correlation between E Mg and S Mg for out-patients, R = 0.29 (p < 0.001). In-patients with infections and pressure sores had significantly raised E Mg concentrations but normal or low S Mg. High E Mg concentrations in illness are likely to be due to alterations in characteristics of the erythrocytes themselves rather than an indication of body magnesium excess. E Mg concentrations in illness should be interpreted with caution.

This study examined the effect of an acute-phase response on plasma trace element concentrations of non-small cell lung cancer (NSCLC) patients. In normal subjects (n = 13) and NSCLC patients (n = 22), fasting concentrations of albumin, C-reactive protein, the trace elements iron, zinc, copper, and selenium, and their associated proteins transferrin, albumin, ceruloplasmin, and glutathione peroxidase were measured. The NSCLC patients were subdivided into two equal groups depending on whether they had a C-reactive protein concentration < 35 mg/l (Group 1) or > 35 mg/l (Group 2). Circulating zinc, iron, and transferrin concentrations were significantly lower in NSCLC Group 1 than in the control group (p < 0.05). Circulating concentrations of iron, zinc, and the binding proteins transferrin and albumin were significantly lower in NSCLC Group 2 than in the control group and NSCLC Group 1 (zinc not significantly different) (p < 0.01). In contrast circulating concentrations of copper and its binding protein ceruloplasmin were significantly increased in NSCLC Group 2 compared with NSCLC Group 1 and the control group (p < 0.01). Additionally, plasma selenium and glutathione peroxidase concentrations were significantly lower (p < 0.05) in NSCLC Group 2 than in NSCLC Group 1 and the control group. In the NSCLC patients there were significant negative correlations between concentrations of C-reactive protein and iron, transferrin, zinc, albumin, and selenium (p < 0.05). Furthermore, there were also significant positive correlations between C-reactive protein and copper (r = 0.788, p < 0.001) and ceruloplasmin (r = 0.831, p < 0.001) concentrations. The presence of an acute-phase response has implications for the interpretation of circulating trace element concentrations, the status of patients with NSCLC, and supplementation with trace elements in patients with NSCLC.

A procedure for the determination of selenium in whole blood and urine has been improved by optimization of the digestion and derivatization procedures. An overnight pre-digestion step with 4 + 1 concentrated nitric-perchloric acids reduced the time of mineralization at 170 degrees C from 4 h to 30-45 min. Conversion of all the selenium to selenite (SeIV) was optimized by addition of 1 ml of concentrated hydrochloric acid, with heating to 100 degrees C for 30 min. The rate of formation of the 2,3-diaminonaphthalene (DAN) complex of selenium was improved by heating to 70-100 degrees C for a minimum of 30 min. Co-addition of hexane during derivatization simplified the extraction procedure. The modified method was applied successfully to the analysis of Seronorm quality control whole blood and urine (83 and 24 micrograms l-1 Se, respectively). Samples from 12 healthy adults, gave results in expected ranges (mean concentrations of 75 +/- 8 micrograms l-1 in blood and 25 +/- 8 micrograms l-1 in urine). The structure of the Se-DAN complex was investigated using elemental analysis, FTIR spectrometry, 1H and 13C NMR spectroscopy, and FAB MS. The information obtained indicates that the selenodiazo group does not contain an Se-O bond or protonated nitrogens, as proposed in other studies.

Two procedures were compared for the determination of citrate in plasma protein solution (PPS). Ion chromatography with gradient elution was preferred to an enzymatic-spectrophotometric method for citrate concentrations in the range 0.4-11 mg l-1. Better comparisons of results by both methods were obtained for citrate concentrations at the g l-1 level, as dilution of the PPS reduced interferences in the enzymatic procedure.

A method has been developed which separates the three major selenium-containing proteins found in human blood serum and plasma: selenoprotein-P, glutathione peroxidase and albumin. They were separated from plasma or serum by affinity chromatography and the Se content determined directly by ETAAS. Selenoprotein-P is retained on a heparin-Sepharose column, and subsequently eluted with an excess of heparin, while glutathione peroxidase is separated by a blue-Sepharose column. The amount of Se associated with albumin was assumed to be the Se remaining in the rest of the sample. The detection limit of the ETAAS method, when applied to the separated fractions, was 0.8 microgram l-1 (2 ng absolute) and the accuracy of the determination was confirmed by comparison with spectrofluorimetry. The distribution of Se in the serum or plasma of 21 healthy people was determined, showing that 53 +/- 6% of the total present is associated with selenoprotein-P, 39 +/- 6% as glutathione peroxidase and 9 +/- 4% as albumin.

A method is described for the direct determination of selenium in serum or plasma by electrothermal atomic absorption spectrometry with deuterium-arc background correction. Samples are diluted (1 + 2) with a modifier containing palladium nitrate and Triton X-100. Samples are atomised from a L'vov platform in a pyrolytically-coated electrographite tube and peak area signals are measured. Direct determination is possible by using selenium standards matched to the physiological concentrations of sodium chloride, calcium and phosphate. The detection limit is 6 micrograms/L in the original sample. Precision at a selenium concentration of 97 micrograms/L was 2.2% RSD within batch and 3.0% RSD between batch. Accuracy is shown by (i) analysis of a Seronorm reference serum (value obtained 97 +/- 3 micrograms/L; recommended value 96 micrograms/L); (ii) recovery of added selenium (93.3 +/- 6.7% and 98.2 +/- 3.3% at additions of 30 and 60 micrograms/L, respectively) and (iii) comparison of results with mean of all laboratories in an external quality assessment scheme.

1. 65Cu/63Cu stable-isotope ratios have been measured in blood serum after oral administration of the stable isotope 65Cu. The incorporation of the isotope into the plasma protein pool was followed at various times for up to 3 days. The resulting patterns of enrichment in healthy control subjects, in Wilson's disease patients and in heterozygotes for the Wilson's disease gene, were similar in appearance to those found by others using copper radioactive isotopes. After an initially high enrichment at 2 h after dosage, the Wilson's disease cases, in contrast to the control subjects, did not show a secondary rise in isotope enrichment of the plasma pool after 72 h, demonstrating a failure to incorporate copper into caeruloplasmin. The Wilson's disease heterozygotes had variable degrees of impairment of isotope incorporation, not always distinguished from those of control subjects. 2. The stability of the isotope also permits the copper tracer to be followed for a longer period. Ten healthy subjects were studied for over 40 days, allowing the biological half-time of an oral dose of copper to be determined (median 18.5 days, 95% confidence interval 14-26 days). Known heterozygotes for the Wilson's disease gene were found to have a significantly increased biological half-time for removal of copper from the plasma pool (median 43 days, 95% confidence interval 32-77 days). 3. The incorporation of 65 Cu in patients with diseases of the liver (other than Wilson's disease) was found to be similar to that in control subjects, aiding differential diagnosis.

Methods for the determination of aluminium in serum, dialysate fluid and water by inductively coupled plasma optical emission spectrometry are described and validated. Aluminium was measured at 167 nm using an argon purged monochromator. Matrix effects in serum and dialysate fluid were overcome by using an yttrium internal standard. Serum was found to have a complicated background in the region of 167 nm: careful selection of the wavelength used for background correction is therefore a pre-requisite for accurate analysis. The method for serum was validated by comparison with electrothermal atomization atomic spectrometry and the limit of agreement determined to be +/- 0.3 mumol/L. Routine performance in a quality assessment scheme has been highly satisfactory for a period of 1 year. The method is ideal for fast and accurate monitoring of patients potentially at risk from aluminium toxicity.

Several papers have reported severe liver disease in association with massive hepatic copper accumulation, which do not seem to be either of the recognised copper associated liver diseases, namely Wilson's disease and Indian childhood cirrhosis. A further case is reported in which novel copper kinetic studies were carried out using the stable isotope 65Cu, showing that this patient did not suffer from Wilson's disease. It is suggested that these cases can be divided into two groups on the basis of age, clinical course, and history of excessive copper ingestion. The benefits of using 65Cu for in vivo studies of copper metabolism is discussed.

To examine the effect of paediatric GI disease on selenium concentration in plasma and glutathione peroxidase activity in plasma and red cells, results in children with Crohn's disease (n = 39), cystic fibrosis (n = 14), intractable diarrhoea (n = 13), and biliary atresia (n = 10) were compared with those from 86 healthy children undergoing routine operations. In Crohn's disease, plasma selenium concentrations were rarely low, but glutathione peroxidase activity was increased in the plasma and reduced in the red cells. Selenium concentration and glutathione peroxidase activity increased with steroid treatment but decreased with a selenium-deficient elemental diet. Plasma selenium concentration was normal in children with cystic fibrosis but very low in severely malnourished children with biliary atresia and intractable diarrhoea. Selenium concentration and glutathione peroxidase activity should be monitored in children with severe malnutrition or requiring prolonged nutritional support. Supplementation is recommended in cases of severe selenium depletion.

Changes in the oral microbial flora, some of which are related to mucosal disease, have been detected in the elderly, but the causes are not fully understood. This study has examined the possible role of micronutrient depletions in the reduced colonisation resistance and oral infection exhibited by some elderly subjects. The oral health, oral microbiology and micronutrient status of 37 geriatric patients aged 65-91 years (mean 81 years) were examined. Ten of the patients had no oral mucosal disease. Mucosal pathology in the remainder included erythema (27%), denture stomatitis (24%), angular cheilitis (16%) and atrophic glossitis (41%). Those with mucosal pathology had significantly lower serum iron concentrations (P = 0.02). Serum or plasma concentrations of zinc, copper, selenium, C-reactive protein, transferrin, caeruloplasmin, albumin, vitamin A and vitamin E were not significantly different between those with oral disease and those with healthy mouths. Similarly, activity of the selenium-containing enzyme, red cell glutathione peroxidase, did not differ significantly between the two groups. In both groups, plasma selenium concentrations (82%), red cell glutathione peroxidase activity (47%), plasma zinc concentrations (58%) and albumin concentrations (44%) tended to be below the lower limit of the reference interval. The influence of subclinical infection on these values is discussed.

In Hamburg, the incidence of reported cases of infectious hepatitis more than doubled from 1990 to 1991. The increase refers to hepatitis A, B and other forms of hepatitis. The seven public health offices and the local ministry for health, works and social affairs in Hamburg have analysed the development in a computer-based retrospective study comparing the 1990 and 1991 data. The predominantly affected age group of hepatitis A shifted from childhood to young adulthood. The importance of travelling to acquire hepatitis A was less than expected. In all forms of hepatitis the large number of IV-drug users and prisoners was striking.

Serum and mononuclear blood cell (MBC) magnesium were measured in 24 healthy community subjects, average age 76 years (67-93), and in 21 ill hospitalized subjects, average age 79 years (65-90). MBC magnesium, expressed as mumol/mg protein, was significantly lower in the in-patient group (P < 0.001), but tended to be higher in the same group when expressed as fmol/cell (not significant). Further samples from community subjects on the same day, and again at 7 days, revealed coefficients of variation for intrasubject analysis of 12% and 22%, respectively (fmol/cell). The equivalent intrasubject values for serum were 2.8% on the same day and 4% at 1 week. MBC magnesium values for inpatients were probably distorted by changes in cell size and cell protein content caused by illness. Biological variability and the effects of illness on the composition and size of cells seem to limit the usefulness of MBC magnesium measurement as a clinical tool for assessment of body magnesium status.

One hundred and thirty patients undergoing elective myocardial revascularisation were randomised to receive an intravenous infusion containing either 50 mmol magnesium chloride or placebo during the first 48 h following surgery. Magnesium was given to 66 patients and a placebo infusion to 64 patients. Postoperative serum magnesium concentrations fell in the placebo group (from 0.83 +/- 0.06 to 0.79 +/- 0.11 mmol/l) but were elevated in the magnesium group (from 0.82 +/- 0.05 to 1.2 +/- 0.25 mmol/l). In total, 35 patients (26.9%) had a supraventricular arrhythmia, of which 11 were in the magnesium group (16.7%) and 24 (37.5%) in the placebo group (P = 0.013). Three patients in the magnesium group had an episode of ventricular fibrillation and three patients in the placebo group had frequent ventricular ectopics. There was one death in the magnesium group associated with a perioperative myocardial infarction. This study shows that intravenous magnesium supplements reduce the incidence of supraventricular arrhythmias following coronary artery surgery.

1. The effects of granisetron (160 micrograms kg-1 body weight) and haloperidol (3 mg) on psychometric performance and the EEG were investigated in a randomised, single-blind, crossover, placebo controlled study of 12 healthy male volunteers. 2. There was evidence that haloperidol impaired psychometric performance; however its effects on the EEG were not clear cut. In contrast there was very little evidence to suggest that granisetron had any impact on performance or the EEG. 3. The findings from this study suggest that granisetron does not impair daytime function and that it can be co-administered with haloperidol without producing unwanted synergistic effects.

Investigation using DNA markers in a family with Wilson disease revealed that an apparently normal child of 10 years of age with non-diagnostic copper biochemistry had the disease. The procedure used linked restriction fragment length polymorphic markers. Demonstration of increased liver copper concentration from a liver biopsy confirmed the diagnosis and the child was started on chelation therapy. Two other asymptomatic siblings were shown, using the same techniques, not to have the disease. Similar analysis was carried out on another family with just one index case.

Incompetent veins in the popliteal fossa were assessed with duplex ultrasound in 123 legs of 104 patients. In 91 cases the venous reflux was the result of a single incompetent vein draining into the deep system. In 32 cases duplex ultrasound demonstrated a combination of incompetent veins. With the exception of 3 patients duplex scanning accurately localised the incompetent veins and their "junctions" with the deep system. In 48 legs the reflux signal, detected in the surface vein, extended back beyond the "junction" into a proximal segment of the popliteal vein or superficial femoral vein; in most cases the distal popliteal vein remained competent. Six distinct venous reflux patterns were identified in the popliteal fossa, which seemed to correlate with the severity of related clinical symptoms.

A single 6-g dose of aluminum hydroxide was given to eight patients on regular hemodialysis before and 3 days after parathyroidectomy (PTX). Serum aluminum levels were measured before and after 5 h after ingestion of aluminum hydroxide to examine indirectly the effects on absorption of aluminum from the gastrointestinal tract of both high and low parathyroid hormone (PTH). Plasma PTH levels fell significantly from 2,724 +/- 1,830 ng/l (mean +/- 1 SD) before PTX to 352 +/- 63 ng/l after PTX. However, no significant change was detected in serum aluminum levels before or after PTX (1.45 +/- 0.96 to 1.92 +/- 0.88 mumol/l before PTX; 2.02 +/- 1.41 to 2.89 +/- 1.19 mol/l after). These findings indicate that in patients with chronic renal failure, high plasma levels of PTH are not associated with significant increases in serum aluminum concentrations after ingestion of a large quantity of aluminum hydroxide. Parathyroid hormone may not enhance intestinal absorption of aluminum in humans.

The prevalence and clinical features of Wilson's disease in Scotland were investigated. Thirty three cases were identified but adequate information was available on only 28. In 1989, the prevalence rate was 4 per million. Ten patients with a mean (SEM) age of 18 (1.9) years presented with neurological symptoms, 12 patients aged 14 (1.7) years presented with hepatic symptoms, and six patients aged 12 (0.9) years were asymptomatic siblings of patients with Wilson's disease. Nine (56%) of the 16 patients who underwent liver biopsy on presentation were found to have cirrhosis. Penicillamine treatment was stopped in nine patients because of: abnormal peripheral blood count (6), rash (2), and patient's own choice (1). Nineteen patients were alive in 1989 -12 were well, one had chronic liver failure, four chronic neurological disabilities, and two had both chronic liver failure and neurological disabilities. Twelve patients died from: complications of chronic liver failure (2), acute liver failure (4), pneumonia associated with immobility (4), and other causes (2). Several patients who died had received incomplete medical supervision.

Concentrations of nine inorganic elements in autopsy samples of kidney, liver, heart and skeletal muscle from 33 aged subjects, mean age 80 years, were compared with concentrations in similar samples from 12 young healthy accident victims, mean age 29 years. Tissue samples were removed within 48 hours of death and dry weight was used as a frame of reference. Potassium and magnesium were significantly lower in muscle (P less than 0.001) and heart tissue (P less than 0.001) of elderly subjects. There was evidence of accumulation of zinc in liver tissue of the elderly (P less than 0.01). Copper was significantly lower in the heart tissue of elderly subjects (P less than 0.001) whereas manganese was lower in both the heart (P less than 0.01) and the kidney tissue (P less than 0.001) of the elderly. Selenium concentrations were lower in the kidney (P less than 0.001) of the elderly. Elderly heart tissue appeared to accumulate chromium (P = 0.007) and aluminium (P less than 0.001). No significant differences were found for iron concentrations between these two populations. These major differences in tissue element concentrations between young and aged subjects merit further attention.

1. Intragastric pH monitoring was performed before and after the single-blind administration of ranitidine or placebo (saline) in eight healthy subjects and four patients with end-stage renal disease who were on regular haemodialysis. 2. The subjects were studied on two occasions and were given aluminum hydroxide (1185 mg) orally 90 min after the administration of ranitidine or saline. 3. Plasma aluminum concentrations and, in normal men, urinary excretion of aluminum were monitored before and after the oral aluminum load. 4. Intragastric pH increased significantly with ranitidine but not with placebo (P less than 0.001). Urinary aluminum excretion increased significantly after the administration of aluminum hydroxide during the placebo phase (P less than 0.001) but not during the ranitidine phase. Plasma aluminium concentrations were higher in the patients with renal failure than in the normal subjects (P less than 0.05), but were unchanged in both groups after the oral aluminium load. 5. This study shows that gastric pH is an important factor in the modulation of aluminum absorption in man, and indicates that reducing gastric acid secretion with ranitidine may reduce the toxicity of orally administered aluminium compounds.

The effects of granisetron (160 micrograms kg-1 body weight) and lorazepam (2.5 mg) on psychometric performance were investigated in a randomized, single-blind, crossover, placebo controlled study of twelve healthy male volunteers. There was strong evidence that lorazepam impaired psychometric performance. In contrast there was very little evidence to suggest that granisetron had any impact on performance or that there was any interaction between the two compounds. The findings from this study suggest that granisetron does not impair psychometric performance and that it can be co-administered with lorazepam without producing unwanted synergistic effects.

1. The EEG effects of granisetron, a potent and selective 5-HT3 receptor antagonist (160 micrograms kg-1), and lorazepam (2.5 mg) were examined in 12 healthy male volunteers. 2. The results indicated that lorazepam had a marked effect on the CNS, significantly increasing power in the slow (1-7 Hz) and fast (13-20 Hz; 21-30 Hz) wavebands whilst reducing power in the mid range (8-12 Hz). 3. In contrast there was no demonstrable effect of granisetron on the EEG at the dose tested, and no evidence of a pharmacodynamic interaction between the two compounds.