Three-dimensional architecture and surface functionality of coccolith base plates.

Coccolithophores are marine phytoplankton that are among the most prolific calcifiers widespread in Earth's oceans, playing a crucial role in the carbon cycle and in the transport of organic matter to the deep sea. These organisms produce highly complex mineralized scales that are composed of hierarchical assemblies of nano-crystals of calcium carbonate in the form of calcite. Coccolith formation in vivo occurs within compartmentalized mineralisation vesicles derived from the Golgi body, which contain coccolith-associated polysaccharides ('CAPs') providing polymorph selection and mediating crystal growth kinetics, and oval organic mineralisation templates, also known as base plates, which promote heterogenous nucleation and further mechanical interlocking of calcite single crystals. Although the function of coccolith base plates in controlling crystal nucleation have been widely studied, their 3D spatial organization and the chemical functional groups present on the crystal nucleation sites, which are two crucial features impacting biomineralization, remain unsolved. Utilising cryo-electron tomography we show that base plates derived from an exemplary coccolithophore Pleurochrysis carterae (Pcar) in their native hydrated state have a complex 3-layered structure. We further demonstrate, for the first time, the edge and rim of the base plate - where the crystals nucleate - are rich in primary amine functionalities that provide binding targets for negatively charged complexes composed of synthetic macromolecules and Ca2+ ions. Our results indicate that electrostatic interactions between the negatively charged biogenic CAPs and the positively charged rim of the base plate are sufficient to mediate the transport of Ca2+ cations to the mineralization sites.

Neutron detection via bubble chambers.

Research investigating the application of pressure-cycled bubble chambers to fast neutron detection is described. Experiments with a Halon-filled chamber showed clear sensitivity to an AmBe neutron source and insensitivity to a (137)Cs gamma source. Bubble formation was documented using high-speed photography, and a ceramic piezo-electric transducer element registered the acoustic signature of bubble formation. In a second set of experiments, the bubble nucleation response of a Freon-134a chamber to an AmBe neutron source was documented with high-speed photography.

Long-term remission of recurrent parvovirus-B associated anemia in a renal transplant recipient induced by treatment with immunoglobulin and positive seroconversion.

Parvovirus B-19 (PVB)-related recurrent anemia is reported in a renal transplant recipient with long-term remission induced by intravenous immunoglobulin and decreasing immunosuppression. Positive plasma polymerase chain reaction (PCR) and intense bone marrow infection were present at diagnosis, despite the absence of serum immunoglobulin IgG and IgM antibodies to the virus. Seroconversion against the virus was followed by long-term remission while the plasma PCR for PVB remained positive. This case illustrates the absence of serum antibodies in an immunosuppressed host despite florid infection with the virus. Positive seroconversion in a naïve subject is associated with long-term remission even in the presence of detectable viral DNA copies in the plasma.

Results of autologous stem cell transplant in multiple myeloma patients with renal failure.

Data are presented on 81 multiple myeloma (MM) patients with renal failure (creatinine > 176.8 micromol/l) at the time of autologous stem cell transplantation (auto-SCT), including 38 patients on dialysis. The median age was 53 years (range: 29-69) and 26% had received more than 12 months of prior chemotherapy. CD34+ cells were mobilized with granulocyte colony-stimulating factor (G-CSF) alone (n = 51) or chemotherapy plus G-CSF (n = 27), yielding medians of 10 and 16 x 106 CD34+ cells/kg respectively (P = 0.003). Sixty patients (27 on dialysis) received melphalan 200 mg/m2 (MEL-200). Because of excessive toxicity, the subsequent 21 patients (11 on dialysis) received MEL 140 mg/m2 (MEL-140). Thirty-one patients (38%) completed tandem auto-SCT, including 11 on dialysis. Treatment-related mortality (TRM) was 6% and 13% after the first and second auto-SCT. Median times to absolute neutrophil count (ANC) > 0.5 x 109/l and to platelets > 50 x 109/l were 11 and 41 d respectively. Non-haematological toxicities included mucositis, pneumonitis, dysrhythmias and encephalopathy. At a median follow up of 31 months, 30 patients have died. Complete remission (CR) was achieved in 21 patients (26%) after first SCT and 31 patients (38%) after tandem SCT. Two patients discontinued dialysis after SCT. Median durations of complete remission (CR) and overall survival (OS) have not been reached; probabilities of event-free survival (EFS) and OS at 3 years were 48% and 55% respectively. Dialysis dependence and MEL dose did not affect EFS or OS. Sensitive disease prior to SCT, normal albumin level and younger age were independent prognostic factors for better OS. In conclusion, renal failure had no impact on the quality of stem cell collections and did not affect engraftment. MEL-140 had an acceptable toxicity and appeared equally effective as MEL-200. In the setting of renal failure, the role of auto-SCT early in the disease course and benefits of tandem SCT require further evaluation.

Sustained low-efficiency dialysis for critically ill patients requiring renal replacement therapy.

BACKGROUND: The replacement of renal function for critically ill patients is procedurally complex and expensive, and none of the available techniques have proven superiority in terms of benefit to patient mortality. In hemodynamically unstable or severely catabolic patients, however, the continuous therapies have practical and theoretical advantages when compared with conventional intermittent hemodialysis (IHD). METHODS: We present a single center experience accumulated over 18 months since July 1998 with a hybrid technique named sustained low-efficiency dialysis (SLED), in which standard IHD equipment was used with reduced dialysate and blood flow rates. Twelve-hour treatments were performed nocturnally, allowing unrestricted access to the patient for daytime procedures and tests. RESULTS: One hundred forty-five SLED treatments were performed in 37 critically ill patients in whom IHD had failed or been withheld. The overall mean SLED treatment duration was 10.4 hours because 51 SLED treatments were prematurely discontinued. Of these discontinuations, 11 were for intractable hypotension, and the majority of the remainder was for extracorporeal blood circuit clotting. Hemodynamic stability was maintained during most SLED treatments, allowing the achievement of prescribed ultrafiltration goals in most cases with an overall mean shortfall of only 240 mL per treatment. Direct dialysis quantification in nine patients showed a mean delivered double-pool Kt/V of 1.36 per (completed) treatment. Mean phosphate removal was 1.5 g per treatment. Mild hypophosphatemia and/or hypokalemia requiring supplementation were observed in 25 treatments. Observed hospital mortality was 62.2%, which was not significantly different from the expected mortality as determined from the APACHE II illness severity scoring system. CONCLUSIONS: SLED is a viable alternative to traditional continuous renal replacement therapies for critically ill patients in whom IHD has failed or been withheld, although prospective studies directly comparing two modalities are required to define the exact role for SLED in this setting.

Ehrlichia chaffeensis in a renal transplant recipient.

Since its first description in human beings in 1986, ehrlichiosis is now increasingly recognized as a cause of tick-borne febrile illnesses. However, the disease has been reported only rarely in immunosuppressed patients. We report a case of human ehrlichiosis in a patient with a cadaveric renal transplant. The diagnosis was confirmed initially by a positive polymerase chain reaction (PCR) for E. chaffeensis. The antibody titer became positive several weeks later. The patient responded promptly to treatment with doxycycline. Ehrlichiosis should be considered in the differential diagnosis of an acute febrile illness in transplant recipients. PCR provides a rapid means to confirm the diagnosis, particularly in settings in which antibody response may be suppressed.

Renal allograft dysfunction associated with cytomegalovirus infection.

Renal transplant recipients are at an increased risk for cytomegalovirus (CMV) infection, which occurs as a primary infection or as a result of reactivation of a latent virus. The main risk factors for symptomatic CMV disease include a CMV-negative recipient of a kidney from a CMV-positive donor (primary infection) and treatment of rejection with monoclonal or polyclonal antibodies. In this study, we report a renal transplant recipient with multiple risk factors for the development of CMV infection. He developed three episodes of CMV disease; the first was associated with gastrointestinal tract involvement, and the second episode was diagnosed according to surveillance laboratory test results in the absence of symptoms. The third episode was associated with acute allograft dysfunction. The renal transplant biopsy specimen showed viral inclusions without acute rejection or glomerular abnormality. Despite the absence of morphological injury on biopsy, treatment of CMV with ganciclovir was accompanied by an improvement in renal function. Further studies are needed to establish the mechanism of allograft dysfunction in the absence of inflammatory changes.

Compromising abnormalities of the brachial plexus as displayed by magnetic resonance imaging.

Magnetic resonance images (MRI) of brachial plexus anatomy bilaterally, not possible by plain radiographs or CT, were presented to the Vascular Surgery, Neurology, and the Neurosurgery departments. Patients were requested for MRI of their brachial plexus. They were referred for imaging and the imaging results were presented to the faculty and housestaff. Our technique was accepted and adopted to begin referrals for MRI evaluation of brachial plexopathy. Over 175 patients have been studied. Eighty-five patients were imaged with the 1.5 Tesla magnet (Signa; General Electric Medical Systems, Milwaukee, WI) 3-D reconstruction MRI. Coronal, transverse (axial), oblique transverse, and sagittal plane T1-weighted and selected T2-weighted pulse sequences were obtained at 4-5 mm slice thickness, 40-45 full field of view, and a 512 x 256 size matrix. Saline water bags were used to enhance the signal between the neck and the thorax. Sites of brachial plexus compromise were demonstrated. Our technique with 3-D reconstruction increased the definition of brachial plexus pathology. The increased anatomical definition enabled the vascular surgeons and neurosurgeons to improve patient care. Brachial plexus in vivo anatomy as displayed by MRI, magnetic resonance angiography (MRA), and 3-D reconstruction offered an opportunity to augment the teaching of clinical anatomy to medical students and health professionals. Selected case presentations (bodybuilder, anomalous muscle, fractured clavicle, thyroid goiter, silicone breast implant rupture, and cervical rib) demonstrated compromise of the brachial plexus displayed by MRI. The MRI and 3-D reconstruction techniques, demonstrating the bilateral landmark anatomy, increased the definition of the clinical anatomy and resulted in greater knowledge of patient care management.

Extracorporeal membrane oxygenation support as a bridge to pediatric heart transplantation.

BACKGROUND: Mechanical circulatory support for intractable heart failure as a bridge to transplantation has been used infrequently in children. The lack of clinically available ventricular assist devices has resulted in the use of conventional extracorporeal circuits with oxygenator as the main modality for circulatory support. In this study we reviewed our experience with extracorporeal membrane oxygenation (ECMO) support in children with irreversible heart failure who were awaiting heart transplantation. METHODS AND RESULTS: Since 1985, 14 children were placed on ECMO support for circulatory failure and were considered candidates for heart transplantation: 8 children had postcardiotomy contractile failure, 3 had dilated cardiomyopathy, and 3 had viral myocarditis. Five of these children had cardiac arrest and were placed on support during cardiopulmonary resuscitation. Mean duration of ECMO support was 109 +/- 20 hours. Eight patients developed pulmonary edema requiring decompression of the left ventricle, 3 by blade atrial septostomy and 5 by left atrial vent cannula. Nine of 14 received a heart transplant, 1 child recovered spontaneously (myocarditis), and 4 died of sepsis on ECMO. Of the children who received transplants, 6 were early survivors with 1 late death (lymphoproliferative disease), for a total of 7 of 14 (50%) early and 6 of 14 (43%) late survivors. CONCLUSIONS: Our experience suggests that ECMO is an effective means of circulatory support as a bridge to transplantation in children. Decompression of the left ventricle is often required to prevent pulmonary edema. Sepsis and bleeding remain a limitation to prolonged mechanical support with ECMO in children.

Significance of a first-time atypical Papanicolaou smear in a young, high-risk African-American and Latino-American population.

The first atypical Papanicolaou smear in young, sexually active Latino and African-American women of low socioeconomic status may be predictive of underlying cervical neoplasia and human papillomavirus infection of significant quantity. The optimal management of first-time atypia on routine Pap smear has not been established. In many clinics, colposcopically directed sampling of the cervix is recommended only if atypia persists following specific or nonspecific treatment of cervicitis or after an arbitrarily determined time interval. Others recommend immediate colposcopic evaluation. To determine the best approach to the first-time atypical Pap smear in young minority women at high risk for the development of cervical cancer, 250 such patients were evaluated with colposcopically directed biopsy of the cervix prior to any form of therapy. Pap smears were repeated at the time of colposcopy. Histologically, there was evidence of cervical intraepithelial neoplasia in 41% of patients and human papillomavirus infection in 86%. Repeat Pap smears predicted the presence of cervical intraepithelial neoplasia in only 24% of patients. Immediate colposcopic evaluation represents the most prudent approach to the first-time atypical Pap smear in young, high-risk minority women.

Extracorporeal membrane oxygenation for cardiac rescue in children with severe myocardial dysfunction.

OBJECTIVE: To assess the experience and efficacy of extracorporeal membrane oxygenation (ECMO) for cardiac rescue in patients with presumptively lethal cardiac dysfunction at the Children's Hospital of Pittsburgh. DESIGN: Retrospective analysis of patient records from a 9-yr period. SETTING: A 22-bed tertiary care pediatric intensive care unit (ICU) with an average of 1,400 admissions per year. An average of 150 open cardiotomy surgeries are performed per year, and all postoperative and severely ill cardiac patients are cared for in the ICU. PATIENTS: A total of 29 pediatric ICU patients with myocardial failure received ECMO throughout the 9-yr study period. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Demographic information, underlying cardiac defect, intraoperative and postoperative data, postoperative course, details of ECMO treatment, and outcome were collected. Comparison of survivors with nonsurvivors was performed using the Mann-Whitney U test for continuous variables. Twenty-three (79%) of 29 patients recovered myocardial function while undergoing ECMO, 18 (62%) of 29 patients were successfully decannulated, and 13 (45%) of 29 patients survived to hospital discharge. Long-term survival rate was 11 (38%) of 29 patients. Three (60%) of five bridge-to-heart transplant patients survived. Eleven (65%) of 17 patients who suffered cardiac arrest before ECMO, survived to discharge and nine (53%) of these 17 patients remain long-term survivors. Survival rate in patients who required cardiac massage for > 15 mins before cannulation was six (55%) of 11 patients. CONCLUSIONS: Patients with severe myocardial dysfunction who fail conventional therapy can be successfully supported with ECMO during the period of myocardial recovery. ECMO can also provide a viable circulatory support system in patients with prolonged cardiac arrest who fail conventional resuscitation techniques. ECMO is also an effective means of support as a mechanical bridge to heart transplantation.

Imaging the hepatic lymphatics: experimental studies in swine.

Magnetic resonance (MR) imaging augmented with 3-D MR reconstruction provides an excellent display of the soft tissues and surface anatomy of the human body. The excellent anatomical detail of MR images makes this radiographic modality an ideal tool to teach anatomy to all health-care professionals. Previous studies of the lung and liver in swine revealed that the hepatic lymphatics communicated with the visceral pleural lymphatics via the so-called pulmonary ligament, which appears as a sheet of visceral pleura containing lymphatics and small blood vessels in the swine model. A review of the surgical operative reports at the UCLA School of Medicine revealed that the hepatic lymphatics are not connected or even ligated during hepatic resections and transplantations. Therefore, the authors hypothesized that the unattached lymphatics may be a cause of postoperative complications and that interruption of these important lymphatic pathways may specifically result in immediate ascites and right pleural effusions. Cannulation of the hepatic lymphatics is proposed as a method to reduce postoperative complications. The purpose of this research is to demonstrate the visual and radiographic display of the hepatic lymphatics in a swine model and to provide a means to teach anatomical-pathological correlation.

Fluoroscopic chest tube insertion and patient care.

Catheters and chest tubes may be placed under fluoroscopic control to reduce pleural effusions. This procedure has been adopted as a routine procedure at the UCLA School of Medicine in Los Angeles, California to improve patient care. This technique was modified for the placement of large chest tubes, which can be placed by a radiologist without multiple attempts or complications. Our experience with 2234 patients who underwent this procedure between 1977 and 1990 is described.

Magnetic resonance imaging of chest wall lesions.

Magnetic resonance imaging (MRI) demonstrates surface anatomy, nerves, and soft tissue pathology. Selective placement of the cursor lines in MRI displays specific anatomy. The MR images can then be used as adjunct in teaching surface anatomy to medical students and to other health professionals. Because the normal surface anatomy could be imaged at UCLA's radiology department, it was decided to image soft tissue abnormalities with MR to assist in patient care. Patients imaged were scheduled for special procedures of the chest or staging lymphangiograms. Patients were placed into categories depending on known diagnosis or interesting clinical presentation. The diagnostic categories included Hodgkin's disease, melanoma, carcinomas (eg, lung or breast), lymphedema, sarcomas, dermatological disorders, and neurological disorders. All images were orchestrated by the radiologist. This article discusses both the teaching and clinical impact on patient care.

Anatomy of the thorax and shoulder girdle displayed by magnetic resonance imaging.

In 1971, radiographic anatomy of the human body was added to the gross anatomy course at UCLA. Radiographic contrast studies and plain anatomical displays were formulated into teaching packages for all organ systems. Residents presented each package to first-year medical students in the dissection laboratory to augment the teaching of anatomy. In November 1984, magnetic resonance imaging was instituted in the radiology department. Imaging the chest produced coronal and axial planes which displayed the muscles and soft tissues of the thorax. In 1986, the authors presented their study of MR anatomy of the chest and shoulder girdle to the American Association of Anatomists. The purpose of this presentation is to demonstrate the anatomy of the thorax and shoulder girdle as displayed by magnetic resonance, correlated with regional anatomy, with emphasis on soft tissue structures.

A rhesus monkey model for sexual transmission of a papillomavirus isolated from a squamous cell carcinoma.

Recently we molecularly cloned and characterized a papillomavirus from a lymph node metastasis of a primary penile carcinoma found in a rhesus monkey; this virus species, rhesus papillomavirus type 1 (RhPV-1), is similar to oncogenic human papillomaviruses (HPVs), such as HPV-16 or HPV-18, in that the RhPV-1 DNA was found to be integrated in the tumor cell DNA. To compare the sexual transmission and oncogenic nature of RhPV-1 with these HPVs, we undertook an extensive retrospective study of a group of rhesus monkeys whose sexual mating and offspring histories were known. These animals had mated directly with the index male mentioned above or were secondarily exposed to this virus through intermediate sexual partners. This study combines cytological, histopathological, and several complementary hybridization and DNA amplification techniques on multiple tissue samples to demonstrate the sexually transmitted nature of RhPV-1. The oncogenic potential of RhPV-1 is suggested in several of the infected animals by the presence of various degrees of neoplasia including squamous cell cancer of the cervix.

Enhancing magnetic resonance images using water bags.

Fascial planes between tissues are separated by connective tissue, fat, and blood vessels. Magnetic resonance imaging displays surface anatomy and soft tissues. Our team has been successful in demonstrating brachial plexus nerves as a model of magnetic resonance anatomy. Radiologists have devised methods to increase the resolution of images by suppressing noise and increasing the sharpness of the image. We added water bags to a 0.3 tesla permanent magnet suppressing the noise and increasing the signal to image our patients. The images proved to be sharper.

Human papillomavirus type 27: detection of a novel human papillomavirus in common warts of a renal transplant recipient.

The cloning and partial characterization of the genome of human papillomavirus type 27 (HPV-27) is described. Hybridization analyses reveal that this is a new HPV type, with the strongest homology to HPV-2.