Current literature and imaging techniques of aseptic lymphocyte-dominated vasculitis-associated lesions (ALVAL).

Aseptic lymphocyte-dominated vasculitis-associated lesions (ALVAL) are a recognized complication of metal-on-metal bearing hip prostheses. There is an impending concern regarding the future investigation and management of patients who have received such implants. The current literature is discussed, and the current guidelines for management of these patients in the UK are reviewed. The various imaging techniques available, such as computed tomography, metal artefact reduction magnetic resonance imaging, and ultrasound are discussed and evaluated with respect to the assessment of patients with suspected ALVAL. The histopathological findings are discussed with images of the tissue changes provided. Images of the radiological findings are also provided for all general radiological methods. ALVAL and its radiological presentation is an important issue that unfortunately may become a significant clinical problem.

Unintended changes in cognition, mood, and behavior arising from cell-based interventions for neurological conditions: ethical challenges.

The prospect of using cell-based interventions (CBIs) to treat neurological conditions raises several important ethical and policy questions. In this target article, we focus on issues related to the unique constellation of traits that characterize CBIs targeted at the central nervous system. In particular, there is at least a theoretical prospect that these cells will alter the recipients' cognition, mood, and behavior-brain functions that are central to our concept of the self. The potential for such changes, although perhaps remote, is cause for concern and careful ethical analysis. Both to enable better informed consent in the future and as an end in itself, we argue that early human trials of CBIs for neurological conditions must monitor subjects for changes in cognition, mood, and behavior; further, we recommend concrete steps for that monitoring. Such steps will help better characterize the potential risks and benefits of CBIs as they are tested and potentially used for treatment.

Solifenacin for overactive bladder in women unsuccessfully treated with immediate release oxybutynin: a pilot study.

The aim of the study was to determine the efficacy, tolerability and cost comparison of solifenacin for women with an overactive bladder (OAB) who failed to respond to immediate release oxybutynin (IR). A standard 3-day bladder diary, cost of incontinence pads used over 4 weeks and a validated OAB quality-of-life questionnaire were collected at baseline, at 4 weeks and at 12 weeks of commencing solifenacin treatment. Nine women were enrolled into the study. Eight of the women completed the 12-week study and one woman withdrew. The mean number of day-time micturitions was 11.4 +/- 2.7 at baseline and 7.3 +/- 3.5 at 12 weeks of solifenacin treatment (p = 0.0002). The mean number of nocturia was 2.8 +/- 1.4 at baseline and 0.9 +/- 0.9 at 12 weeks of solifenacin treatment (p = 0.0004). The total number of incontinence episodes per day was 4.9 +/- 4.6 at baseline and 1.9 +/- 2.7 at 12 weeks of solifenacin treatment (p = 0.02). The mean micturition volumes were 160 +/- 50 ml at baseline and 280 +/- 50 ml at 12 weeks of solifenacin treatment (p = 0.002). The symptom severity domain of the OAB-questionnaire (OAB-q) showed a value of 60.8 +/- 23.0% at baseline and 32.0 +/- 25.9 % at 12 weeks of solifenacin treatment (p = 0.001). The health-related quality-of-life (HRQL) domain of the OAB-q showed a value of 45.5 +/- 28.0% at baseline and 73.3 +/- 24.8% at 12 weeks of solifenacin treatment (p = 0.0006). This study shows a significant improvement in bladder diary and validated quality-of-life parameters with solifenacin in women with urge incontinence who have previously failed to respond to or have been intolerant of oxybutynin IR.

Sarcoplasmic reticulum. IX. The permeability of sarcoplasmic reticulum membranes.

Fragmented sarcoplasmic reticulum (FSR) membranes isolated from rabbit skeletal muscle are impermeable to inulin-(14)C (mol wt 5,000), and dextran-(14)C (mol wt 15,000-90,000) at pH 7.0-9.0, yielding an excluded space of 4-5 microl/mg microsomal protein. In the same pH range urea and sucrose readily penetrate the FSR membrane. EDTA or EGTA (1 mM) increased the permeability of microsomes to inulin-(14)C or dextran-(14)C at pH 8-9, parallel with the lowering of the FSR-bound Ca(++) content from initial levels of 20 nmoles/mg protein to 1-3 nmoles/mg protein. EGTA was as effective as EDTA, although causing little change in the Mg(++) content of FSR. The permeability increase caused by chelating agents results from the combined effects of high pH and cation depletion. As inulin began to penetrate the membrane there was an abrupt fall in the rate of Ca(++) uptake and a simultaneous rise in ATPase activity. At 40 degrees C inulin penetration occurred at pH 7.0 with 1 mM EDTA and at pH 9.0 without EDTA, suggesting increased permeability of FSR membranes. This accords with the higher rate of Ca(++) release from FSR at temperatures over 30 degrees C. The penetration of microsomal membranes by anions is markedly influenced by charge effects. At low ionic strength and alkaline pH acetate and Cl are partially excluded from microsomes when applied in concentrations not exceeding 1 mM, presumably due to the Donnan effect. Penetration of microsomal water space by acetate and Cl occurs at ionic strengths sufficiently high to minimize charge repulsions.

Seasonality of vitamin D status and bone turnover in patients with Crohn's disease.

BACKGROUND: While winter-time vitamin D deficiency has been well-documented in Crohn's disease patients, less is known about vitamin D status during summertime and whether a seasonal variation exists in bone turnover. AIMS: To compare vitamin D status and bone turnover markers in Crohn's disease patients with age- and sex-matched controls during late-summer and late-winter. SUBJECTS: Crohn's disease patients (n = 44; mean age 36.9 years, currently in remission) and matched controls (n = 44) were recruited from Cork University Hospital and Cork City area, respectively. METHODS: Bloods were analysed for 25-hydroxyvitamin D, parathyroid hormone, bone-specific alkaline phosphatase, osteocalcin and urine analysed for N-telopeptides of type 1 collagen. RESULTS: Serum 25-hydroxyvitamin D concentrations were significantly (P < 0.003) lower in Crohn's disease patients than in control subjects during both seasons. In Crohn's disease patients, serum 25-hydroxyvitamin D concentrations were lower (P < 0.0001) whereas serum parathyroid hormone, osteocalcin and bone-specific alkaline phosphatase and urinary N-telopeptides of type 1 collagen levels were higher (P < 0.001) during late-winter than late-summer. CONCLUSION: There were notable seasonal variations in vitamin D status and bone turnover markers in Crohn's disease patients. The impact of winter decline in vitamin D status and increase in bone turnover on long-term risk of osteopenia/osteoporosis in Crohn's disease patients is unclear.

Microalbuminuria in NIDDM.

OBJECTIVE: To determine an effective screening procedure for microalbuminuria. RESEARCH DESIGN AND METHODS: The prevalence of microalbuminuria in NIDDM patients whose urine was negative on routine Albustix testing was studied. Microalbuminuria was measured in overnight urine samples from 128 NIDDM patients on at least two of three occasions over a 6-mo period. Patients were tested with Micro-Bumintest or Micral-Test. RESULTS: Ten of 128 patients had albumin concentrations > or = 20 mg/L on two or more occasions, 14 patients had A-C ratios > or = 3 mg/M on two or more occasions, and 9 patients had both. CONCLUSIONS: Neither Micro-Bumintest nor Micral-Test is a useful or feasible screening procedure for microalbuminuria.

Magnetic resonance imaging of intestinal necrosis in preterm infants.

BACKGROUND AND OBJECTIVE: Noninvasive diagnosis of intestinal necrosis is important in planning surgery in preterm infants with necrotizing enterocolitis (NEC). We aimed to assess the potential of magnetic resonance imaging (MRI) for the diagnosis of intestinal necrosis. STUDY PARTICIPANTS AND METHODS: Abdominal MRI scans were performed in a group of preterm infants with suspected NEC and compared with surgical findings and to MRI results in a group of control infants. In addition, MRI was performed in 2 preterm infants with suspected NEC who did not require surgery. RESULTS: Six infants with a median birth weight of 1220 g (range, 760-1770 g) and median gestational age at birth of 30 weeks (range, 28-34 weeks) were studied at a median postnatal age of 10 days (range, 4-19 days). Four infants had a bubble-like appearance in part of the intestinal wall, intramural gas, and an abnormal fluid level within bowel lumen. At surgery, NEC was found in 5 infants and sigmoid volvulus in 1. The site of the bubble-like appearance corresponded to the site of intestinal necrosis at surgery. Four control infants with a median birth weight of 1500 g (range, 730-2130 g) and a median gestational age of 31 weeks (range, 26-36 weeks) had abdominal MRI at a median postnatal age of 8 days (range, 4-70 days). None of the above findings were seen in any control infant. The bubble-like appearance was not seen in the 2 infants with suspected NEC who did not require surgery. CONCLUSION: Abdominal MRI allows the noninvasive diagnosis of bowel necrosis. This may aid the timing of surgical intervention in preterm infants with a clinical diagnosis of NEC.gangrene, ischemia, MRI, necrotizing enterocolitis.

Predictive factors for long-term engraftment of autologous blood stem cells.

Data from 170 consecutive patients aged 19-66 years (median age 46 years) who underwent unmanipulated autologous blood stem cell transplant (ASCT) were analyzed to determine if total CD34+ cells/kg infused, CD34+ subsets (CD34+41+, CD34+90+, CD34+33-, CD34+38-, CD34+38-DR-), peripheral blood CD34+ cell (PBCD34+) count on first apheresis day, or various clinical factors were associated with low blood counts 6 months post ASCT. Thirty-four patients were excluded from analysis either because of death (n = 17) or re-induction chemotherapy prior to 6 months post ASCT (n = 13), or because of lack of follow-up data (n = 4). Of the remaining 136 patients, 46% had low WBC ( < 4 x 10(9)/l), 41% low platelets (<150 x 10(9)/l), and 34% low hemoglobin ( < 120 g/l) at a median of 6 months following ASCT. By Spearman's rank correlation, both the total CD34+ cell dose/kg and the PBCD34+ count correlated with 6 month blood counts better than any subset of CD34+ cells or any clinical factor. The PBCD34+ count was overall a stronger predictor of 6 month blood counts than was the total CD34+ cells/kg infused. Both factors retained their significance in multivariate analysis, controlling for clinical factors. In conclusion, subsets of CD34+ cells and clinical factors are inferior to the total CD34+ cell dose/kg and PBCD34+ count in predicting 6 month blood counts following ASCT.

Unrelated donor BMT recipients given pretransplant low-dose antithymocyte globulin have outcomes equivalent to matched sibling BMT: a matched pair analysis.

Fifty-seven patients receiving unrelated donor (UD) BMT were matched for disease and stage with 57 recipients of genotypically matched related donor (MRD) BMT. All UD recipients were matched serologically for A and B and by high resolution for DR and DQ antigens. All patients received CsA and 'short course' methotrexate with folinic acid. Unrelated donor BMT patients also received thymoglobulin 4.5 mg/kg (6 mg/kg if <30 kg) in divided doses over 3 days pretransplant. For UD and RD BMT, respectively, incidence of acute GVHD grade II-IV was 19 +/- 6% vs 36 +/- 8%, grade III-IV 10 +/- 6% vs 18 +/- 7%, chronic GVHD 44 +/- 8% vs 51 +/- 8%, non-relapse mortality 15 +/- 5% vs 8 +/- 4% at 100 days, 28 +/- 8% vs 36 +/- 7% at 3 years. At 3 years, relapse was 45 +/- 7% vs 42 +/- 7%, and disease-free survival 39 +/- 7% vs 37 +/- 7%. None of these differences are significant. Three-year overall survival was identical at 42 +/- 7%. For 29 patients with low/intermediate risk leukemia, disease-free survival was 68 +/- 10% after UD BMT vs 59 +/- 9% for RD BMT recipients (P = NS). Corresponding figures for high risk patients were 14 +/- 7% and 21 +/- 8%, respectively. We conclude that UD BMT recipients matched as above and given pretransplant ATG have similar outcomes to recipients of MRD BMT using conventional drug prophylaxis. Unrelated donor BMT should be considered in any circumstance where MRD BMT is routine.

Highly fructose selective transport promoted by boronic acids based on a pentaerythritol core.

We have designed and synthesized a highly lipophilic boronic acid (11) with a molecular shape that makes it much more effective at carrying sugars through organic membranes than a previously used steroidal boronic acid. The corresponding diboronic acid (12) was also found to transport fructose ahead of glucose with a very high selectivity (7.6:1.0). Modeling suggests that 12 is able to carry two fructose molecules at once in a complex stabilized through hydrogen bonding and ion pairing.

Survival of free DNA encoding antibiotic resistance from transgenic maize and the transformation activity of DNA in ovine saliva, ovine rumen fluid and silage effluent.

To assess the likelihood that the bla gene present in a transgenic maize line may transfer from plant material to the microflora associated with animal feeds, we have examined the survival of free DNA in maize silage effluent, ovine rumen fluid and ovine saliva. Plasmid DNA that had previously been exposed to freshly sampled ovine saliva was capable of transforming competent Escherichia coli cells to ampicillin resistance even after 24 h, implying that DNA released from the diet could provide a source of transforming DNA in the oral cavity of sheep. Although target DNA sequences could be amplified by polymerase chain reaction from plasmid DNA after a 30-min incubation in silage effluent and rumen contents, only short term biological activity, lasting less than 1 min, was observed in these environments, as shown by transformation to antibiotic resistance. These experiments were performed under in vitro conditions; therefore further studies are needed to elucidate the biological significance of free DNA in the rumen and oral cavities of sheep and in silage effluent.

Characterisation of a Rrhodobacter sphaeroides gene that encodes a product resembling Eescherichia coli cytochrome b(561) and R. sphaeroides cytochrome b(562).

Analysis of the photoactive yellow protein (pyp) gene region of Rhodobacter sphaeroides has revealed the presence of an additional open reading frame, orfD, that had not previously been identified. Here we report the location of this new gene and the predicted amino acid sequence of the encoded protein. The translation product resembles a group of small cytochrome b-like proteins, including Escherichia coli cytochrome b(561), R. sphaeroides cytochrome b(562), and two new cytochrome b(561)-like proteins identified using the E. coli genome sequence, for which functions have not yet been established. To determine OrfD function in R. sphaeroides, an orfD mutant was constructed. The OrfD mutant exhibited growth rates and yields very similar to those of the wild-type strain when grown under a variety of growth conditions. Respiration rates, reduced-minus-oxidised spectra and levels of photosynthetic complexes were also very similar in the two strains. Although the role of OrfD was therefore not determined here, we demonstrate that the orfD gene is expressed in R. sphaeroides under aerobic, semi-aerobic and photosynthetic growth conditions.

Major injury as a unique opportunity to initiate treatment in the alcoholic.

A prospective study was performed on the use of a standard outpatient intervention technique to induce inpatient alcoholic trauma patients into accepting alcoholism treatment. Interventions were performed on 17 trauma patients. All patients who underwent intervention accepted treatment and were immediately transferred to a 28-day inpatient treatment facility. Alcoholic trauma patients are highly susceptible to intervention for their disease. We found that intervention performed upon discharge from the trauma service successfully initiates alcoholism treatment.

Elevated serum angiotensin converting enzyme levels in metastatic ovarian dysgerminoma.

A case of a 32-year-old XY genotype female is described, presenting with mediastinal and abdominal lymphadenopathy and associated with an elevated serum angiotensin I converting enzyme (SACE) level. Lymph node histology showed a malignant dysgerminoma of ovarian origin. Combined chemotherapy led to a radiological regression of the lymphadenopathy and coincided with a decrease in SACE concentration. The authors suggest that SACE may be a marker for disseminated germinoma tumours and may be useful for monitoring treatment.

Enzyme linked immunosorbent assay (ELISA) for the determination of protein-A.

A competitive ELISA for the determination of protein-A concentration in culture supernatants is described. The sensitivity of the assay is 50 ng/ml and it may be used to determine concentrations of protein-A up to 1000 ng/ml. The assay is specific, rapid and suitable for routine screening of protein-A producing microorganisms.

Adapting the uricase/peroxidase procedure for plasma urate to reduce interference due to haemolysis, icterus or lipaemia.

The estimation of serum urate by uricase/peroxidase procedures involving single point bichromatic absorbance monitoring gives inaccurate results with samples which are haemolysed, icteric or lipaemic. These inaccuracies can be greatly minimized by reducing the rate of chromogen formation and applying the assay in a kinetic mode.

A robust procedure for the automated measurement of total serum bilirubin using potassium ferricyanide.

Bilirubin is oxidized to biliverdin by 1.0 mmol/L potassium ferricyanide in the presence of caffeine. The absorbance decline at 480 nm with blanking at 660 nm is proportional to bilirubin concentration. The assay is linear up to 1000 mumol/L and is suitable for the measurement of bilirubin in adult and neonatal patients. The assay is accurate and precise and is not significantly affected by haemolysis up to 5.0 g/L haemoglobin. Reagents and calibration are stable for at least 3 months.

Simple adaptation of the Technicon SMAC system to operate 18 channels with reduced volumes of plasma.

The Technicon SMAC system was adapted to function with much smaller volumes of plasma than those used in standard procedures. With only minimal operator-entered changes to the 7.6 computer program, and simple modifications of the glucose and alkaline phosphatase channels, the SMAC analyser performed equally well when the plasma volume was decreased from 235 microliter sequentially down through 176 microliter, 142 microliter, and 105 microliter. The basic principle employed was to maintain a constant flow rate of diluted sample plus diluent with decreasing sample size. The instrument proved to have the capability of operating successfully on all channels with lower signals than those encountered with the unmodified system.

Ultrasonic heating of the brain of the fetal sheep in utero.

The fetal sheep was used as a model to determine the extent of ultrasound-induced heating of brain tissue in procedures involving pulsed Doppler examination of fetal intracranial arteries. Temperature measurements were recorded in late-gestation fetuses insonated in utero. The centre frequency was 3.5 MHz and a pulse repetition rate of 6 to 10 kHz produced a power output of 0.6 or 2 W. The brain was insonated in the near field of a focussed beam where the -6-dB beam width was 1.7 cm for the 0.6-W transducers and 1.2 cm for the 2-W transducers. Mean (standard error) maximal temperature increases of 3.0 degrees C (0.3) and 12.5 degrees C (1.3), respectively, were recorded in dead fetuses. The mean values obtained in normally perfused living fetuses were lower by 43% and 30%, respectively, showing that vascular perfusion substantially limited ultrasonic heating in sheep fetal brain tissue. There were no changes in blood flow to the heated brain tissue as measured using radiolabelled microspheres.

The influence of variations in blood flow on pulsed doppler ultrasonic heating of the cerebral cortex of the neonatal pig.

Pulsed Doppler ultrasound examination of the fetal cerebral circulation may cause potentially harmful temperature elevations in brain tissue immediately beneath the insonated segment of the skull. This study measured the effect of variations in cerebral blood flow on ultrasonic heating of the cerebral cortex of anaesthetised, neonatal pigs. Wide and narrow ultrasound beams were used. Pulsed ultrasound exposures were delivered in 90 s bursts at 5.8 micros pulse length, pulse repetition frequency 8 kHz and centre frequency 3.5 MHz. Studies were performed with the target at the focus of a fixed, stationary beam of 0.3 cm -6 dB beam width (narrow beam) and I(spta) 1.4 W/cm(2) (n = 11), or with the target in the near field of a fixed, stationary beam of 1.6 cm -6 dB beam width (wide beam) and I(spta) 3.6 W/cm(2)(n = 5). The 90 s ultrasound exposures were performed under three different conditions of ambient cerebral blood flow: baseline (during normocarbic, normoxic conditions), increased (during hypercarbic, hypoxic conditions) and absent (postmortem). Cerebral blood flow was measured using the radiolabelled microsphere technique. In the narrow beam studies, cerebral blood flow during baseline was 34 +/- 4 ml/min/100 g, rising to 109 +/- 32 ml/min/100 g during the increased phase (p < 0.001); in the wide beam studies baseline flows were 29 +/- 9 ml/min/100 g, whereas flows in the increased phase were 128 +/- 32 ml/min/100 g (p < 0.001). There was no difference in the heating curves for normal, increased and absent cerebral blood flow for exposure to the narrow beam, when mean temperature increases of 1.5 degrees C at 90 s were recorded in each case (p > 0.21, power > 0.8). However, the heating curves for the wide beam were significantly different for the three rates of blood flow with mean temperature increases of 1.9 degrees C (normal flow), 1.7 degrees C (increased flow) and 2.4 degrees C (no flow) recorded at 90 s (p < 0.05).