A new look at the heart-novel imaging techniques.

The development and successful implementation of cutting-edge imaging technologies to visualise cardiac anatomy and function is a key component of effective diagnostic efforts in cardiology. Here, we describe a number of recent exciting advances in the field of cardiology spanning from macro- to micro- to nano-scales of observation, including magnetic resonance imaging, computed tomography, optical mapping, photoacoustic imaging, and electron tomography. The methodologies discussed are currently making the transition from scientific research to routine clinical use, albeit at different paces. We discuss the most likely trajectory of this transition into clinical research and standard diagnostics, and highlight the key challenges and opportunities associated with each of the methodologies.

How useful is routine amniotic fluid and neonatal surface swab microbiology at Caesarean section?

BACKGROUND: Our aim was to evaluate the clinical impact of routine amniotic fluid and neonatal surface swab microbiology at Caesarean section. MATERIALS AND METHODS: Microbiology data from 1 537 neonates delivered by Caesarean section were analysed in the light of clinical outcome. RESULTS: 1 340 (87%) neonates had non-pathogenic bacteria or negative culture results from both amniotic fluid and surface swab samples. Of the 197 (13%) neonates with pathogenic bacteria, 22 (1.4%) were diagnosed with infection, but only in 6 (0.4%) were the bacteria presumed to be responsible for the infection. Amniotic fluid and surface swab culture had sensitivities of 54% and 35%, and positive predictive values of 14% and 17%, respectively, for detecting a neonate at risk of infection. CONCLUSION: Amniotic fluid and neonatal surface swab microbiology at Caesarean section contributes little if anything to postnatal management and can be safely dropped from operative routine.

Continuous independent quality control for fetal nuchal translucency measurements provided by the cumulative summation technique.

PURPOSE: The cumulative summation technique (CUSUM) is an innovative method for the quality control of nuchal translucency (NT) measurements. CUSUM allows immediate corrective intervention as soon as an unacceptable tendency is noted. The aim of this study was to implement an objective and dynamic quality control method based on the CUSUM technique for prompt analysis of fetal NT measurement which would be compatible with different standards in routine clinical practice. The findings were compared to the standard NT quality control methods currently in use. MATERIALS AND METHODS: Three sets of fetal NT measurements performed by three experienced examiners (I, II and III) were selected for retrospective evaluation. One additional set of NT measurements performed by examiner IV was prospectively assessed to approve the practicability of the method. NT measurements were conducted according to the recommendations of Fetal Medical Foundation (FMF) Germany and London. NT values were converted to Z-scores. For quality and accuracy evaluation, data were fed into the Digisono CUSUM software to create double CUSUM charts of Z-scores. In addition, histograms were composed from the Z-scores of each set of measurements and plotted against a normal Gaussian distribution. RESULTS: Three different patterns of retrospective performance and one set of NT measurements that was evaluated prospectively are presented. The full alignment of Z-scores using CUSUM curves reflected exact periods of under- and overestimation of NT measurements. The CUSUM chart of the prospective data set reveals that prompt corrective intervention of poor performance resulted in reconstitution of optimal results and provided sufficient control. In contrast, histograms of NT Z-scores only showed a minor positive or negative shift as compared to the expected values on the basis of Gaussian distribution, but could not identify poor performance. CONCLUSION: Use of the CUSUM technique analysing the quality of sonographic NT measurements provides the possibility to prospectively observe the development of the examiner's skills, to maintain competence and to promptly define the time when inaccurate measurements start to occur.

Impact of the time window on plasma volume measurement with indocyanine green.

Recent reports have questioned the accuracy of the indocyanine green dilution technique for measuring plasma volume. Our objective was to evaluate the impact of different time windows for monoexponential extrapolation. We retrospectively analysed 31 indocyanine green decay curves to investigate the problem in principle (group 1) and prospectively performed another 21 plasma volume measurements to estimate its practical impact (group 2). To monoexponentially extrapolate back to the specific extinction at the time of dye injection, two different time windows were applied to each decay curve, comparing the plasma volumes resulting from sampling within a short (5 min) period of time. Extrapolating back from the longer period led to a higher apparent plasma volume relative to the shorter period in both groups, the difference being 348 +/- 171 ml (group 1) and 384 +/- 131 ml (group 2; mean +/- SD; p < 0.05 each). This result was due to a reliable monoexponentiality of decay only up to the 5th min after dye injection. Thus, to estimate the initial distribution space of indocyanine green via monoexponential extrapolation, the first linear kinetic of indocyanine green decay should be taken.

[Current recommendations for the treatment of iron deficiency anemia]. / Recommandations actuelles pour le traitement de l'anémie ferriprive.

Iron deficiency is a frequent complication in chronically ill patients and in pregnant women. Iron status can now be characterised precisely and relatively easily by determining serum ferritin, transferritin saturation and if necessary hypochromic erythrocytes and the haemoglobin content of erythrocytes (CHr). Oral iron replacement is usually restricted by limited absorption and low tolerability. Intravenous iron therapy is possible in such cases and can be combined with rHuEPO (e.g. EPREX/ epoetin alfa) in severe cases. Iron saccharate (VENOFER) is commercially available in Switzerland and this permits high dose iron replacement without any danger of anaphylaxis or acute iron toxicity.

Estimation of phenotypic and genetic parameters for weight gain and weight at fixed ages in the double-muscled Belgian Blue Beef breed using field records.

In the double-muscled Belgian Blue beef (DM-BBB) breed, selection focuses on muscular conformation and not on weight gain and higher weight. There are very few studies on growth in the DM-BBB using field records. Therefore, farms have no available useful figures on weight at fixed ages and weight gain for the DM-BBB. This study describes and evaluates live weights of DM-BBB animals. All the data were gathered on farms in Belgium. It was found that a male DM-BBB weighs an average of 51 kg at birth, 98 kg at 3 months, 242 kg at 7 months, 430 kg at 13 months and 627 kg at 20 months. Between the age of 7 and 20 months, weight gain is more than 1200 g a day. Females weigh 47 kg at birth, 96 kg at 3 months, 189 kg at 7 months and 332 kg at 13 months. For males, estimates of heritability for weights at 7, 13 and 20 months were between 0.21 and 0.36. The heritability for weight gain between 13 and 20 months was 0.13. This demonstrates that it is possible to select for higher weights and for increased growth between 13 and 20 months. Animals having high weights at a young age (7 and 13 months) tend to have also high weight at slaughtering age (20 months; r(g) between 0.81 and 0.98), but no additional growth between 13 and 20 months (r(g) between -0.09 and 0.00). High weight at 20 months is partially due to growth between 13 and 20 months (r(g) = 0.49).

[The iron letter--an update on the treatment of iron deficiency anemia]. / Eisenbrief--Aktuelle Empfehlungen zur Therapie der Eisenmangelanämie.

Iron deficiency is a frequent complication in chronically ill patients and in pregnant women. Iron status can now be characterised precisely and relatively easily by determining serum ferritin, transferritin saturation and if necessary hypochromic erythrocytes and the haemoglobin content of erythrocytes (CHr). Oral iron replacement is usually restricted by limited absorption and low tolerability. Intravenous iron therapy is possible in such cases and can be combined with rHuEPO (e.g. EPREX/Epoetin alfa) in severe cases. Iron saccharate Switzerland and this permits high dose iron replacement without any danger of anaphylaxis or acute iron toxicity.

Evaluation of PCR testing of ethanol-fixed nasal swab specimens as an augmented surveillance strategy for influenza virus and adenovirus identification.

Viral culture isolation has been widely accepted as the "gold standard" for laboratory confirmation of viral infection; however, it requires ultralow temperature specimen storage. Storage of specimens in ethanol at room temperature could expand our ability to conduct active surveillance and retrospective screenings of viruses with rapid and inexpensive real-time PCR tests, including isolates from remote regions where freezing specimens for culture is not feasible. Molecular methods allow for rapid identification of viral pathogens without the need to maintain viability. We hypothesized that ethanol, while inactivating viruses, can preserve DNA and RNA for PCR-based methods. To evaluate the use of ethanol-stored specimens for augmenting surveillance for detection of influenza viruses A and B and adenoviruses (AdV), paired nasal swab specimens were collected from 384 recruits with febrile respiratory illness at Fort Jackson, S.C., in a 2-year study. One swab was stored at ambient temperature in 100% ethanol for up to 6 months, and the other swab was stored at -70 degrees C in viral medium. For viral detection, frozen specimens were cultured for a variety of respiratory viruses, and ethanol-fixed specimens were tested with TaqMan (TM) probe and LightCycler SYBR green (SG) melting curve assays with at least two different PCR targets for each virus. The sensitivities of the TM and SG assays on specimens stored in ethanol for 1 month were 75% and 58% for influenza A, 89% and 67% for influenza B, and 93 to 98% and 57% for AdV, respectively. Lower specificities of the real-time assays corresponded to the increased detection of PCR-positive but culture-negative specimens. Influenza virus RNA was detected as well or better after 6 months of storage in ethanol.

Effect of postpartum iron supplementation on red cell and iron parameters in non-anaemic iron-deficient women: a randomised placebo-controlled study.

OBJECTIVE: To investigate the effect of oral iron on postpartum red cell and iron parameters in non-anaemic women with iron deficiency. DESIGN: Randomised study of supplementation with oral iron sulphate 80 mg daily or placebo for 12 weeks starting 24-48 hours after delivery, with visits antepartum and 1, 4, 6 and 12 weeks postpartum. SETTING: Swiss university hospital obstetric unit. PARTICIPANTS: Fifty-two women with antenatal iron deficiency (serum ferritin <15 microg/L) and no antenatal or postnatal anaemia (haemoglobin >11 g/dL up to 48 hours before delivery, and >10 g/dL postpartum), divided into two groups comparable in antenatal iron status. METHODS: Supplementation was started 24-48 hours after delivery (visit 1:V1). Additional tablets were issued one week after V1 (V2), four weeks after V1 (V3) and six weeks after V1 (V4). The last visit took place 12 weeks after visit 1 and 6 weeks after visit 4 (V5). Patients were required to return blisters and boxes whether they were used and unused at each visit and compliance was assessed by counting the tablets. Blood samples for haematology and iron status testing were taken before delivery and at each visit. MAIN OUTCOME MEASURES: Iron status (serum ferritin, hypochromic red cells, iron, transferrin saturation, soluble transferrin receptor concentration); erythropoiesis (standard parameters, including reticulocyte indices); and inflammatory response (serum neopterin, C-reactive protein, white cell count) in five-datapoint profiles. RESULTS: Increased ferritin (P= 0.0004) and transferrin saturation (P= 0.03), decreased soluble transferrin receptors (P= 0.02); increased haemoglobin (P= 0.02) and decreased hypochromic red cells (P= 0.04) compared with placebo at 12 weeks, with no differences in other red cell or reticulocyte parameters. There was a positive correlation between C-reactive protein and postpartum ferritin. No correlation was observed in the puerperium between C-reactive protein and hypochromic red cells or soluble transferrin receptors. CONCLUSIONS: Haemoglobin levels and iron stores in women with term gestational iron deficiency benefit significantly from iron supplementation compared with placebo, even in an industrialised population.

Haemoglobinopathy in pregnancy: diagnosis and treatment.

Haemoglobinopathies differ in geographic prevalence but together are amongst the most common genetic disorders worldwide. Despite huge diagnostic progress, therapeutic options remain limited, with many treatments still at the experimental stage, no more so than in pregnancy: not only does the presence of a fetus subject treatments to greater limitations, but also any worsening of the anaemia as pregnancy progresses results in higher fetomaternal morbidity and mortality. Anaemia weakens the response to peripartum blood loss, with the risk of postpartum complications. Until recently the standard conventional therapy for severe anaemia was (repeated) blood transfusion, with its well-known risks. Recombinant human erythropoietin (rhEPO) can induce fetal haemoglobin and is a safer, if less immediately effective, alternative for the correction of anaemia in pregnant patients with haemoglobinopathy.

Impact of parturition on iron status in nonanaemic iron deficiency.

BACKGROUND: Iron-deficient nonanaemic parturients risk underdiagnosis as a result of the reliance on postpartum ferritin and haemoglobin as markers of iron status. Ferritin is an acute-phase protein whose levels increase during the inflammatory response, as occurs after delivery. Our aims were to evaluate the impact of parturition on iron status, erythropoiesis and the inflammatory response, and identify the optimal parameters and timing for diagnosing iron deficiency in the presence of postpartum inflammation. MATERIALS AND METHODS: Conventional parameters of iron status, erythropoiesis and the inflammatory response (serum ferritin, serum iron, transferrin saturation, C-reactive protein) were compared with more recent parameters [soluble transferrin receptors (sTfR), hypochromic red cells, reticulocyte indices] within 48 h either side of delivery in 64 iron-deficient nonanaemic women (defined by a prepartum serum ferritin < or =15 microg L(-1), and a pre- and postpartum haemoglobin of > or =11.0 g dL(-1) and > or =10.0 g dL(-1), respectively). RESULTS: Mean sTfR decreased pre to postpartum from 7.3 to 5.8 microg mL(-1) (P<0.01), while mean serum ferritin increased from 9.7 to 16.9 microg L(-1) (P<0.01). Serum ferritin did not correlate with haemoglobin pre or postpartum (r=0.04, P=0.7; r=0.2, P=0.09), but a correlation persisted postpartum between hypochromic red blood cells and haemoglobin (r=-0.26; P<0.05). The percentage of hypochromic red cells remained virtually unchanged pre- and postpartum (4.0% vs. 3.8%; NS). Postpartum mean reticulocyte haemoglobin content (CHr) was 27.1 +/- 1.6 pg. CONCLUSION: Iron status should be tested prepartum, in the absence of an inflammatory response, rather than in the early postpartum. A valuable additional parameter, where available, might be the hypochromic red cell percentage, which is virtually uninfluenced by the inflammatory response. Furthermore, hypochromic red cell percentage, CHr and sTfR can be helpful to differentiate between functional iron deficiency and depleted iron stores.

Cutaneous fibropapilloma in a mountain lion (Felis concolor).

A 12-yr-old mountain lion (Felis concolor) developed a 0.5-cm3 raised nonpigmented and nonulcerated mass between the lip and the nasal planum. The tumor was surgically removed and diagnosed histologically as a fibropapilloma. The tumor recurred 1 yr later, at which time it was again excised, and the diagnosis was reconfirmed by biopsy. Frozen tissue from the second excision was submitted for polymerase chain reaction testing for papillomavirus. The 176-base pair polymerase chain reaction product recovered from the tumor was cloned and sequenced. The papillomavirus had 96% homology with a papillomavirus previously retrieved from a fibropapilloma in a domestic cat and is the next most closely related to bovine papillomavirus type 1. This is the first report of a virus-associated fibropapilloma in a mountain lion.

Camelid mucoutaneous fibropapillomas: clinicopathologic findings and association with papillomavirus.

Five camelid mucocutaneous fibropapillomas with histologic features similar to equine sarcoids were diagnosed. They were characterized by a dermal fibroblastic proliferation and overlying, often ulcerated hyperplastic epidermis with thin rete pegs extending down into the dermis. Two of the tumors came from llamas and three from alpacas. Four of the animals were 6-year-old females. The fifth was a 6-year-old castrated male. The fibropapillomas were located on the nose, lip, and cheeks. One of the llama tumors waxed and waned before surgery and recurred and spread after surgery. None of the other tumors recurred. All five tumors were positive for papillomavirus (PV) DNA by polymerase chain reaction testing. Nucleotide sequence analysis of the PCR product from one of the llama fibropapillomas confirmed a unique PV. This report provides the microscopic and clinical features of fibropapillomas in camelids as well as evidence for a PV etiology.

Applying molecular biological techniques to detecting biological agents.

Recent efforts in the civilian and military health care and public health communities are directed at strengthening surveillance systems and our national laboratory capabilities for early detection of infectious disease outbreaks. These new systems will address proper specimen collection, transport, nucleic acid processing, molecular assay diagnostic reagent and equipment development, and standardization for sensitive and rapid detection of bioagents in blood and other clinical samples. A greater understanding of the genetic diversity and virulence factors for each organism that could be used for bioterrorism would aid design of rapid molecular detection strategies. Combinations of appropriate diagnostic technologies (culture, immunoassay, and molecular assay) can provide rapid diagnostic response capabilities to microbial threats with antimicrobial resistant organisms, new emerging infectious disease agents, and possible agents of bioterrorism.

Primary effusion lymphoma with herpesvirus 8 DNA in patients coinfected with HIV and hepatitis C virus: a report of 2 cases.

The primary effusion lymphoma (PEL), commonly described in patients with AIDS, is a unique subset of diffuse large cell lymphoma in which the malignant lymphocytes proliferate exclusively in serous cavities. The cytologic, immunophenotypic, and molecular features of PEL are presented from findings of 2 patients coinfected with HIV and hepatitis C virus who presented with abdominal pain. Abdominal radiography in both patients displayed marked peritoneal effusions. Cytomorphologic examination of peritoneal fluid revealed a malignant lymphoma in both. Their immunophenotypic expression was CD30 (Ki-1) and epithelial membrane antigen. Molecular analysis demonstrated human herpesvirus 8 DNA in both patients and bcl-2 oncogene rearrangement within the major breakpoint region of t(14;18) chromosome translocation in Case B only. Clinical correlation supports the current concept that PEL represents a primary HIV/AIDS-related lymphoma in effusion. Cytomorphologic examination of body cavity fluid serves as a tool for the initial diagnosis of PEL.

Feline cutaneous fibropapillomas: clinicopathologic findings and association with papillomavirus infection.

Twenty-three feline cutaneous fibropapillomas with histologic features similar to equine sarcoids were diagnosed. They were characterized by dermal fibroblastic proliferation with overlying, often ulcerated hyperplastic epidermis. Electron microscopic findings supported the fibroblastic nature of the neoplastic cells. The 23 tumors came from 20 cats and were submitted from veterinary clinics in Wisconsin and Minnesota. These tumors occurred most commonly in young cats and were found primarily on the head, neck, and digits. Fifteen of the 17 cats for which breed was reported were domestic shorthair cats. In 11/20 cases, there was confirmed exposure to cattle. Local recurrence of the tumor following surgical excision was reported in 7 of the 18 cats for which follow-up information was available. Metastasis was not documented in any of the cases. Two of the 19 tumors tested by polymerase chain reaction (PCR) had no amplifiable DNA. The remaining 17 were positive for papillomavirus by PCR. No papillomavirus DNA was detected in three other feline skin tumors (cutaneous mast cell tumor, malignant lymphoma, and fibrosarcoma) that served as controls. This is the first report of detection of papillomavirus in feline tumors that have clinicopathologic features similar to equine sarcoids.

Hemoglobin concentration in multiple versus singleton pregnancies--retrospective evidence for physiology not pathology.

OBJECTIVE: To describe hemoglobin (Hb) levels and percentiles for multiple pregnancies and to compare them with reference ranges of singleton pregnancies as published by the Center for Disease Control. STUDY DESIGN: Maternal hemoglobin and red cell indices were compared: (a) between multiple and singleton pregnancies of our hospital and (b) with trimester-specific cut-offs for singleton pregnancies obtained from literature. RESULTS: While early pregnancy hemoglobin values were similar in multiple and singleton pregnancies, second trimester values decreased much faster in multiple pregnancies. Nadir in multiple pregnancies was reached in weeks 24-28 of gestation. In the third trimester mean hemoglobin values were higher in multiple pregnancies, while 5th and 10th percentile were still lower compared to singleton pregnancies at term. The mean whole-pregnancy hemoglobin exceeded the Center for Disease Control (CDC) cut-off for anemia in singleton pregnancies (fifth percentile) and red cell indices remained constant. CONCLUSION: We conclude that with a significantly lower fifth percentile than introduced by the CDC in all trimesters, there should be different cut-offs for anemia in multiple pregnancies considered. A more pronounced decrease in multiple pregnancy hemoglobin levels seems to be physiological.

Common metastatic carcinoma of California sea lions (Zalophus californianus): evidence of genital origin and association with novel gammaherpesvirus.

Tissues from 10 adult California sea lions (Zalophus californianus, seven females and three males) that had metastatic carcinoma in sublumbar area lymph nodes were examined histologically. A distinctive epithelial proliferative lesion interpreted as intraepithelial neoplasia was found in genital tracts of all ten animals; in vagina (5/7), cervix (7/7), uterus (3/7), penis (3/3) and prepuce (3/3). Intraepithelial neoplasia closely resembled metastatic carcinomas and was directly contiguous with invasive carcinoma in one animal. Rare eosinophilic intranuclear inclusion bodies were found in penile and preputial intraepithelial neoplasia (one animal), cervical intraepithelial neoplasia (one animal), invasive cervical carcinoma (one animal) and metastatic carcinoma (two animals). Electron microscopic examination of tissues from two sea lions (one with intraepithelial neoplasia and one with metastatic carcinoma) demonstrated viral particles consistent with a herpesvirus. An immunohistochemical stain for the latent membrane protein of Epstein-Barr virus was positive in intraepithelial neoplasia in one sea lion. Herpesvirus DNA sequences were detected by consensus primer polymerase chain reaction (PCR) in metastatic carcinomas from all four sea lions from which unfixed tumor samples were available. Results of sequencing were consistent with a novel gammaherpesvirus in the genus Rhadinovirus. DNA extracted from the four metastatic carcinomas also was tested for papillomavirus by Southern blot and PCR with consensus papillomavirus primers; all samples were negative by both methods. These findings support the genital origin of the sea lion carcinoma and implicate a novel gammaherpesvirus as a possible cause.