Surveillance of Treated and Untreated Funguria in a University Hospital

Study Objective . To determine the influence of treatment on the microbiologic outcome of funguria. Design . Retrospective case series. Setting . A 300-bed tertiary care teaching hospital in a large metropolitan area. Subjects . 141 hospitalized patients, 18 years of age or older, with at least one urine culture positive (≥ 10² cfu/ml) for fungi. Interventions . Retrospective review of medical records to determine the microbiologic outcome of funguria. Main Results . Funguria developed rapidly in individuals with known predisposing factors. Urinalysis did not routinely detect the presence of fungi or pyuria. Symptoms such as fever, dysuria, and frequency were generally absent. Funguria persisted whether it was due to Candida albicans or non-albicans species. There were no statistical differences in the microbiologic outcomes of treated and untreated funguria. Conclusions . Funguria is a rapidly developing, often benign and persistent process. Minimizing predisposing risks, such as removing indwelling urinary catheters, is beneficial in its management. Pharmacologic treatment of funguria due to C. albicans or non-albicans species does not influence the microbiologic outcome.     

Disposition of Tablet and Capsule Formulations of Digoxin in the Elderly

Study Objective . To compare digoxin tablets and liquid-filled capsules with respect to excretion of the drug and its metabolites in urine and feces at steady state. Design . A randomized, crossover trial, each period lasting 3 weeks, with no washout period. Setting . A university hospital. Patients . Six patients, five of whom were elderly, with histories of gastrointestinal disorders, such as hypochlorhydria, intestinal bacterial overgrowth, and inflammatory bowel disease. Interventions . The patients received digoxin once/day in either tablet or capsule form for 3 weeks, and then were switched to the other formulation. Total urinary and fecal excretion from the last 3 days of each regimen were analyzed for the drug and metabolites. Measurements and Main Results . No statistically significant differences were found between tablets and capsules in recovery of digoxin or its metabolites in urine or feces (p=0.05). One subject had a 4-fold increase in urinary drug excretion and 50% decrease in fecal excretion after taking the capsules compared with tablets. Intersubject variability in extent and type of metabolite excretion was greater than intrasubject variability. Conclusions . Fecal analyses may be an accurate way to classify patients as formers of digoxin reduction products.     

Evidence for the presence of a non-catecholamine, clonidine-displacing substance in crude, methanolic extracts of bovine brain and lung

In the present study we have prepared crude, methanolic extracts of bovine lung and bovine brain and, using radioligand binding assays in conjunction with a number of simple chromatographic techniques, provided evidence for the presence of a non-catecholamine ’clonidine-displacing substance‘ (CDS). The level of CDS in lung extracts (9?units/g wet weight n=11) is approximately 3 times that in the brain extracts. Furthermore, the effect of the crude, methanolic extracts are selective for non-adrenoceptor, imidazoline (labelled by [ ³H]-idazoxan) and a ₂-adrenoceptor binding sites (labelled by [ ³H]-clonidine); both extracts are 5–10-fold more potent displacers of ligand binding to a ₂-adrenoceptors compared with binding to opiate receptors (labelled by [ ³H]-etorphine) and practically inactive against a ₁-adrenoceptor and muscarinic binding sites (labelled by [ ³H]- prazosin and [ ³H]-quinuclidinyl benzilate, respectively). With the exception of the non-adrenoceptor, imidazoline binding assay, which used rat kidney membranes labelled by [ ³H]-idazoxan in the presence of the a ₂-adrenoceptor antagonist RS-15385-197, all radioreceptor assays involved bovine cerebral cortex membranes. Although the extracts contain catecholamines (brain only), histamine (lung only) and monovalent cations (both), which have the potential to interfere with the radioligand binding assays, their concentrations were too low to account for the effects observed. Preliminary attempts at purification of the extracts revealed that CDS activities from the two tissues are similar, i.e., practically insoluble in organic solvents at room temperature, not affected by either Sep-Pak C ₁₈ column or anion exchange resins but retained (along with the monovalent cations) by cation exchange resin. However, following chromatographic separation on a Biogel P2 column, the CDS-containing eluates are cation-free and exhibit qualitatively similar elution profiles. Future experiments will involve further purification of ’clonidine-displacing substance‘ to characterize its interaction with a ₂-adrenoceptor binding sites in greater detail and establish whether it has biological activity consistent with the properties implied by its effects in radioligand binding assays.     

Inter- and intra-individual variability of non-invasive tear break-up time in Hong Kong Chinese

Non-invasive tear break-up time (NITBUT) has been proposed as a measure of tear film integrity which is superior to the more commonly used tear break-up time (TBUT), since it does not alter the volume or the physicochemical properties of the tear layer by the addition of fluorescein. We measured NITBUT by measuring the time taken for distortions or discontinuities to appear in the reflected image of a grid pattern which covered about 80 per cent of the corneal surface. NITBUT measures were made 100 times on seven Hong Kong Chinese subjects with up to 20 consecutive measures being made on a single day. We also measured NITBUT on one occasion on an unselected population of 52 Hong Kong Chinese subjects. NITBUT shows a skewed distribution in all subjects, with many shorter values and some extremely long values. There are statistically significant variations in NITBUT from day to day, and from subject to subject. The group of 52 subjects also had a skewed NITBUT distribution with many short values and some very long values. The arithmetic mean does not adequately represent NITBUT data, either for individual subjects or for this group of subjects. As many as five to eight measures may be necessary to gain a stable estimate of the NITBUT and stability of the measure is improved if extreme values are omitted. We recommend the use of nonparametric statistics to compare NITBUT values from day to day in or between subjects.     

1/T1 rho and low-field 1/T1 of tissue water protons arise from magnetization transfer to macromolecular solid-state broadened lines.

We argue that, for solutions of immobilized protein and for tissue, the dependence of 1/T1 of solvent protons on B(0) at low fields and 1/T1 rho on B1 for all B(0) are both manifestations of the same underlying phenomena: magnetization transfer between mobile water protons and solid-state broadened protein proton levels. Broadening causes rapid mixing of spin orientation within the transverse plane, at all B(0), unless B1 is greater than the protein internal field; this affects 1/T1 rho of solvent protons by magnetization transfer. Similarly, decreasing B(0) below the internal field mixes all orientations of magnetization, which affects the solvent proton low-field 1/T1 and high-field 1/T2.     

DNA probe technology: implications for service planning in Britain

For certain genetic conditions DNA testing identifies carriers and determines the risk status of foetuses, thus helping parents to make more informed prenatal decisions. Data, collected from three genetic centres in England and Wales from August 1986 to July 1990, are used to describe trends in demand for DNA testing, the impact of DNA tests on carrier risk assessment, and the use of DNA tests in relation to pregnancy outcome. Altogether the data include 23,388 subjects and 681 pregnancies in 8738 families divided into five cohorts by year of entry and referral. The most frequent gene disorders referred to the genetic centres are currently being tested or will soon be tested. For these disorders the initial high level of activity has declined and may have reached steady state. Demand for DNA services is high for cystic fibrosis and Duchenne muscular dystrophy, intermediate for Huntington's disease, and low for adult polycystic kidney disease, phenylketonuria and tuberous sclerosis. Based on these findings we suggest that demand for DNA tests will be high in serious, untreatable and slow progressing conditions with early onset; intermediate for conditions affecting intellect and neurological integrity with later onset; and low for treatable, late-onset conditions, or those for which there is evidence of heterogeneity, and variable penetrance. It would be helpful to assess the extent to which this view of demand is confirmed when the new disorders being DNA tested are considered and for the pattern of activity of DNA testing for some types of cancer. Since no DNA centre could offer a fully comprehensive testing service, it is recommended that a structure is created to audit overall activity, assist in policy formulation, and influence supraregional service organisation, in order that the spread of DNA services be planned as effectively as possible. This structure would facilitate monitoring of the evolution of contract specifications agreed by commissioners and providers on a regional basis.     

The risk of cytomegalovirus infection in seronegative transfusion recipients not receiving exogenous immunosuppression

We studied 637 transfusion recipients seronegative for cytomegalovirus (CMV) in the following categories: neonates; pregnant women; and patients experiencing trauma, burns, cardiovascular surgery (adult or pediatric), major surgery, or gastrointestinal hemorrhages. Cultures and serological tests were used to follow up subjects for evidence of CMV infection for a period of three months after their last transfusion. Six (0.9%) developed CMV infection. No significant differences in risk among patient categories were observed. Infected patients received a significantly larger mean number of units of cellular blood products (CBP; 50.0 +/- 38.9 vs. 6.2 +/- 8.5; P less than .001) and plasma (23.7 +/- 15.3 vs. 2.6 +/- 4.6, P less than .001) than did uninfected patients. This result represents a risk per unit of CBP transfused of 0.14%, or approximately 0.38% per unit of seropositive CBP transfused. We observed, however, that patients exposed to CBP from greater than 30 donors had a higher risk of acquiring CMV infection than would be predicted if infectious units were randomly distributed among all donors (P less than .01).     

Human metabolism of arsenobetaine ingested with fish

1. Six volunteers ingested 74As-labelled arsenobetaine with a fish meal. The retention and distribution of the tracer were studied by body radioactivity measurements. 2. The tracer became rapidly dispersed in soft tissues, with no major concentration in any localized organ or region. 3. In all subjects less than 1% of the ingested activity remained in the body after 24 days. 4. Any losses from the skin were minor in relation to those by other routes of excretion.