Pump-probe X-ray holographic imaging of laser-induced cavitation bubbles with femtosecond FEL pulses.

Cavitation bubbles can be seeded from a plasma following optical breakdown, by focusing an intense laser in water. The fast dynamics are associated with extreme states of gas and liquid, especially in the nascent state. This offers a unique setting to probe water and water vapor far-from equilibrium. However, current optical techniques cannot quantify these early states due to contrast and resolution limitations. X-ray holography with single X-ray free-electron laser pulses has now enabled a quasi-instantaneous high resolution structural probe with contrast proportional to the electron density of the object. In this work, we demonstrate cone-beam holographic flash imaging of laser-induced cavitation bubbles in water with nanofocused X-ray free-electron laser pulses. We quantify the spatial and temporal pressure distribution of the shockwave surrounding the expanding cavitation bubble at time delays shortly after seeding and compare the results to numerical simulations.

Social media and organ donation: Ethically navigating the next frontier.

As the organ shortage continues to grow, the creation of social media communities by transplant hospitals and the public is rapidly expanding to increase the number of living donors. Social media communities are arranged in myriad ways and without standardization, raising concerns about transplant candidates' and potential donors' autonomy and quality of care. Social media communities magnify and modify extant ethical issues in deceased and living donation related to privacy, confidentiality, professionalism, and informed consent, and increase the potential for undue influence and coercion for potential donors and transplant candidates. Currently, no national ethical guidelines have been developed in the United States regarding the use of social media to foster organ transplantation. We provide an ethical framework to guide transplant stakeholders in using social media for public and patient communication about transplantation and living donation, and offer recommendations for transplant clinical practice and future research.

Unusual gastric mucosal infiltration by a medullary thyroid carcinoma: a case report.

BACKGROUND: Medullary thyroid carcinoma accounts for approximately 1 to 2 % of all thyroid carcinoma cases. The most common route of dissemination is to locoregional lymph nodes. Distant metastases commonly affect bones, lungs, and liver. We present a case of a white woman with a 25-year history of medullary thyroid carcinoma on multiple medications including tyrosine kinase inhibitor therapy for the last 11 months, who exhibited unusual diffuse infiltration of advanced stage medullary thyroid carcinoma to her gastric mucosa. CASE PRESENTATION: A 53-year-old white woman presented with increasing fatigue, loss of appetite, and severe epigastric pain radiating to her back. She had a history of medullary thyroid carcinoma (pT2pN1b), diagnosed 25 years ago and treated by complete thyroidectomy and repeated bilateral cervical lymph node dissection. Medical therapy included octreotide 20 mg every 4 weeks, which was switched to the tyrosine kinase inhibitor vandetanib 300 mg/day 11 months ago when computed tomography scanning revealed progressive mediastinal lymph node and diffuse and symptomatic pulmonary metastases. Of note, she demonstrated macroscopically stable pulmonary and mediastinal lymph node metastases; however, her calcitonin serum levels dramatically increased. Computed tomography scanning revealed a single new intrahepatic lesion (4 mm) as well as multiple (>10) new supraclavicular lesions suggestive of medullary thyroid carcinoma progress. As proven by gastric biopsy and immunohistochemical evaluation, her epigastric pain was explained by a diffuse infiltration of her gastric mucosa by metastatic medullary thyroid carcinoma. Subsequently, she rapidly deteriorated and died. CONCLUSIONS: The current case report shows for the first time an unusual metastatic infiltration of the gastric mucosa by medullary thyroid carcinoma. When treating these patients, it is important to include this differential diagnosis during follow-up.

[Epithelial neuroendocrine tumors of the upper respiratory tract: New entities, new perspectives]. / Neuroendokrine epitheliale Tumoren des oberen Respirationstrakts : Neue Entitäten, neue Blickwinkel.

Epithelial neuroendocrine tumors of the upper respiratory tract are rare and are classified as typical and atypical carcinoid versus small cell neuroendocrine carcinoma. Furthermore, a giant cell variant of neuroendocrine carcinoma is suggested corresponding to the bronchopulmonary system as well as a recently described subtype of oropharyngeal small cell neuroendocrine carcinoma associated with human papillomavirus. Many arguments relying on clinical as well as on molecular findings indicate that the distinction between carcinoid and poorly differentiated neuroendocrine carcinoma does not only reflect different degrees of differentiation of otherwise related tumors but indicates the existence of substantially different types of neoplasms.

Molecular classifiers for acute kidney transplant rejection in peripheral blood by whole genome gene expression profiling.

There are no minimally invasive diagnostic metrics for acute kidney transplant rejection (AR), especially in the setting of the common confounding diagnosis, acute dysfunction with no rejection (ADNR). Thus, though kidney transplant biopsies remain the gold standard, they are invasive, have substantial risks, sampling error issues and significant costs and are not suitable for serial monitoring. Global gene expression profiles of 148 peripheral blood samples from transplant patients with excellent function and normal histology (TX; n = 46), AR (n = 63) and ADNR (n = 39), from two independent cohorts were analyzed with DNA microarrays. We applied a new normalization tool, frozen robust multi-array analysis, particularly suitable for clinical diagnostics, multiple prediction tools to discover, refine and validate robust molecular classifiers and we tested a novel one-by-one analysis strategy to model the real clinical application of this test. Multiple three-way classifier tools identified 200 highest value probesets with sensitivity, specificity, positive predictive value, negative predictive value and area under the curve for the validation cohort ranging from 82% to 100%, 76% to 95%, 76% to 95%, 79% to 100%, 84% to 100% and 0.817 to 0.968, respectively. We conclude that peripheral blood gene expression profiling can be used as a minimally invasive tool to accurately reveal TX, AR and ADNR in the setting of acute kidney transplant dysfunction.

[Bethesda classification of fine needle punctures of the thyroid. Much ado about nothing really new?]. / Bethesda-Klassifikation der Feinnadelpunktion der Schilddrüse. Viel Lärm um wenig Neues?

The Bethesda system for reporting thyroid cytopathology was published in 2008 (Baloch et al. 2008, Cytojournal 5:6; Baloch et al. 2008, Diagn Cytopathol 36:425-437) offering a classification system which is closely related to clinical data. The aim was to ensure adequate terminology without risk of errors in understanding, to advise clinicians concerning therapeutic options in relationship to cytological diagnoses as well as to facilitate the comparison of cytology data at national and international levels. However, mainly due to specific US American (both medical and legal) demands, this classification system is not yet fully appreciated in most European countries. The reasons are various: (a) Criteria for representative material are much more restrictive than those commonly used and in Germany a higher number of (unnecessary) repunctures would be the consequence. (b) It remains doubtful whether the introduction of a new and rather heterogeneous category of "atypia of undetermined significance or follicular lesion of undetermined significance" would contribute to a substantial decrease of findings classified as "follicular neoplasia". Furthermore it is unlikely that clinicians would be willing to accept the recommended conservative approach with repuncture if a new diagnostic category is associated with a calculated risk of malignancy in 5-15% cases. (c) Until now an integration of new developments in molecular markers into the Bethesda system is missing. Thus, for experienced cytologists the Bethesda system for reporting thyroid cytopathology offers very limited benefits in comparison to the currently used, established and highly accepted classification systems. However, a positive argument remains the fact that an internationally accepted classification system may improve the comparability of the results of national and international studies on thyroid findings.

Changes in gene expression in the permissive larval host lightbrown apple moth (Epiphyas postvittana, Tortricidae) in response to EppoNPV (Baculoviridae) infection.

Host cell and virus gene expression were measured five days after per os inoculation of 3rd instar lightbrown apple moth (LBAM) larvae with the Epiphyas postvittana nucleopolyhedrovirus (EppoNPV). Microarray analysis identified 84 insect genes that were up-regulated and 18 genes that were down-regulated in virus-infected larvae compared with uninfected larvae. From the 134 viral open reading frames represented on the microarray, 81 genes showed strong expression. Of the 38 functionally identifiable regulated insect genes, 23 coded for proteins that have roles in one of five processes; regulation of transcription and translation, induction of apoptosis, and maintenance of both juvenility and actin cytoskeletal integrity. Of the 34 functionally identifiable viral genes that were most strongly expressed, 12 had functions associated with these five processes, as did a further seven viral genes which were expressed at slightly lower levels. A survey of the LBAM-expressed sequence tag library identified further genes involved in these processes. In total, 135 insect genes and 38 viral genes were analysed by quantitative polymerase chain reaction. Twenty-one insect genes were strongly up-regulated and 31 genes strongly down-regulated. All 38 viral genes examined were highly expressed. These data suggest that induction of apoptosis and regulation of juvenility are the major 'battlegrounds' between virus and insect, with the majority of changes observed representing viral control of insect gene expression. Transcription and translational effects seem to be exerted largely through modulation of mRNA and protein degradation. Examples of attempts by the insect to repel the infection via changes in gene expression within these same processes were, however, also noted. The data also showed the extent to which viral transcription dominated in the infected insects at five days post inoculation.

Cerebral venous thrombosis in young adults: 2 Case reports.

Cerebral venous thrombosis (CVT) is a disease with multiple known etiologies that present with a remarkably wide spectrum of clinical signs and symptoms. We present a case of a 34-year-old man with a history of meningeal symptoms for 1 week after receiving a lumbar injection for lower back pain. He subsequently developed dense right hemiplegia and global aphasia. Head magnetic resonance imaging revealed superior sagittal sinus thrombosis. The patient was started on intravenous heparin but deteriorated neurologically. Urokinase infusion directly into the superior sagittal sinus was performed, with striking functional and neurologic improvement. Lupus anticoagulant was positive. We also present the case of a 24-year-old pregnant woman who developed an acute onset of meningeal symptoms and resultant left hemiparesis. Head magnetic resonance angiography revealed thrombosis of right transverse and sigmoid sinuses. Protein S deficiency was found. She was started on intravenous heparin, then enoxaparin, with improvement in symptoms. These cases demonstrate that CVT can be a cause of stroke in young patients with hypercoagability disorders, and a heightened awareness of CVT will promote optimal medical care and functional outcomes. Excellent functional recovery is likely with early recognition and treatment of the underlying etiology, as well as successful lysis of the clot.

Immunocytological analysis of leukocyte subpopulations in urine specimens before and after prostatic massage.

OBJECTIVE: To evaluate the presence of leukocyte subpopulations in urine after prostatic massage (VB 3) in symptomatic patients with > or =10 leukocytes/high power field (magnification x1,000) in expressed prostatic secretions, and who were classified as suffering from chronic bacterial prostatitis or inflammatory chronic pelvic pain syndrome. METHODS: 115 consecutive patients were investigated. Granulocytes in centrifuged midstream urine (VB 2) and VB 3 were counted after Papanicolaou stain. Macrophages, B and T lymphocytes were analyzed after immunocytological staining with monoclonal antibodies according to the alkaline phosphatase anti-alkaline phosphatase method. The counts were quantified as the number of cells per view field at a magnification of x400. In all patients, acute or chronic urethritis had been excluded before enrollment in the study. 16 men without signs or symptoms of urogenital inflammation served as controls. RESULTS: Of the 115 patients, 101 men demonstrated > or =10 leukocytes/view field in VB 3. In comparison to VB 2, the leukocyte subpopulations in VB 3 demonstrated an increase in granulocytes (9.2-fold), macrophages (7.6-fold), T lymphocytes (7.6-fold), and B lymphocytes (4-fold). The increase was statistically significant (p<0.001 each). The proportion of these cells in VB 3 was 81.6, 11.1, 5.5, and 1.8%, respectively. As compared to controls, all leukocyte subsets in VB 3 were significantly elevated (p>0.001 each). CONCLUSION: Elevated numbers of leukocytes in VB 3 are indicative of prostatitis provided that urethral inflammation and leukocyturia in VB 2 are excluded. Granulocytes are the predominant cell type of inflammation. The increase in macrophages, T and B lymphocytes in prostatic secretions indicate the participation of both the cellular and humoral immune system in the inflammatory process.

Microarray analysis of diurnal and circadian-regulated genes in Arabidopsis.

Plants respond to day/night cycling in a number of physiological ways. At the mRNA level, the expression of some genes changes during the 24-hr period. To identify novel genes regulated in this way, we used microarrays containing 11,521 Arabidopsis expressed sequence tags, representing an estimated 7800 unique genes, to determine gene expression levels at 6-hr intervals throughout the day. Eleven percent of the genes, encompassing genes expressed at both high and low levels, showed a diurnal expression pattern. Approximately 2% cycled with a circadian rhythm. By clustering microarray data from 47 additional nonrelated experiments, we identified groups of genes regulated only by the circadian clock. These groups contained the already characterized clock-associated genes LHY, CCA1, and GI, suggesting that other key circadian clock genes might be found within these clusters.

Changing indications for pediatric cholecystectomy.

PURPOSE: The purpose of this study was to determine indications for gallbladder surgery and risk factors for urgent surgery. METHODS: We reviewed all patients <19 years old, who underwent cholecystectomy between 1980 and 1996. RESULTS: There were 128 patients (mean age: 10 years). Fifty-two patients had an underlying hematologic disorder, 47 had another medical disorder, and 29 had no preexisting illness or identifiable risk factor for gallstone disease. Twenty-five percent (32/128) of cholecystectomies were performed urgently. Postoperative complications developed in 5 of 32 patients (16%) who underwent emergency surgery and 6 of 96 patients (6%) who underwent elective surgery. There were 3 deaths, all occurring in patients undergoing emergency cholecystectomy (odds ratio: 23). Furthermore, all who died had congenital heart disease (odds ratio: 183), making congenital heart disease an independent risk factor for gallstone-related mortality. CONCLUSIONS: Cholecystectomy is recommended when medically possible for children with underlying medical diseases. Patients with medical disorders that make them a high surgical risk can be followed clinically, realizing that if urgent surgery is necessary, the morbidity is relatively high. Those children with congenital heart disease and gallstones are at a prohibitively high risk for death after urgent cholecystectomy. For these patients, the risk of an elective cholecystectomy may be acceptable when weighed against the high risk of complications from their gallstones.

The triad of substance abuse, violence, and depression are interrelated in pregnancy.

A study group of 271 registrants had their medical and social history taken by a nurse-interviewer and were requested to take the Substance Abuse Subtle Screening Inventory. If the nurse interviewer felt that the patient needed social service assessment, referral was made, and a social worker completed the the Social Service Review Questionnaire. The patients who were reported as positive for substance abuse did not respond differently from their negative counterparts for issues of demographics, pregnancy, social support, and career. They were highly likely to have had a history of severe depression and/or have been a victim of physical and/or sexual abuse. On the basis of these data we recommend that the prenatal patient who responds positively in her personal history regarding any of these three experiences should be carefully evaluated for problems related to the other two.

Monitoring genome-wide expression in plants.

When completed this year, the Arabidopsis genome will represent the first plant genome to be fully sequenced. This sequence information, together with the large collection of expressed sequence tags, has established the basics for new approaches to studying gene expression patterns in plants on a global scale. We can now look at biology from the perspective of the whole genome. This revolution in the study of how all genes in an organism respond to certain stimuli has encouraged us to think in new dimensions. Expression profiles can be determined over a range of experimental conditions and organized into patterns that are diagnostic for the biological state of the cell. The field of genome-wide expression in plants has yet to produce its fruit; however, the current application of microarrays in yeast and human research foreshadows the diverse applications this technology could have in plant biology and agriculture.

Surgery of the complete atrioventricular canal: relationship between age at operation, mitral regurgitation, size of the ventricular septum defect, additional malformations and early postoperative outcome.

The perioperative risk after repair of the complete atrioventricular canal is reported to be low provided there is a balanced relationship of both ventricles, and elevated pulmonary vascular resistance has been demonstrated to be reversible. However, some pre- and perioperative conditions may adversely affect early postoperative outcome. A consecutive series of 42 patients (mean age 8.5 months, 34/42, 81%, with trisomy 21) operated between 1994 and 1998 was analyzed prospectively for pre- and perioperative risk factors. Echocardiography alone was performed in 35 patients whereas cardiac catheterization was performed in 7 patients aged more than 18 months to confirm operability. Additional malformations were found in 20 patients. Early mortality was 2.3% (1/42), and postoperatively a low cardiac output was observed in 25 patients (59%); NO inhalation was used in 12 patients. Only the size of the ventricular septal defect (> than the diameter of the aortic annulus) could be identified as a predictor of adverse postoperative outcome in multivariate analysis. The presence of associated intracardiac malformations showed a trend to increased perioperative risk in multivariate analysis. Early results after repair of the complete atrioventricular canal are excellent. Survival, postoperative morbidity and normalization of pulmonary artery pressure can be related to the size of the ventricular septal defect. Continuous monitoring of the pulmonary artery pressure (with consequent NO application when indicated) is probably responsible for the low perioperative risk encountered in this series, despite the high incidence of postoperative pulmonary artery hypertension.

Postoperative ad lib feeding for hypertrophic pyloric stenosis.

PURPOSE: The aim of this study was to compare three methods of postoperative feeding after pyloromyotomy for hypertrophic pyloric stenosis (HPS). METHODS: The authors reviewed retrospectively the charts of 308 patients who underwent pyloromyotomy for HPS from 1984 to 1997. Nineteen patients had prolonged hospitalization for other reasons and were excluded from the study, leaving 289 patients for analysis. All procedures were performed by a single group of pediatric surgeons. The individual preferences of these surgeons resulted in three different feeding schedules: R, strictly regimented (>12 hours nothing by mouth, then incremental feeding over > or =24 hours), I, intermediate (>8 hours nothing by mouth, then incremental feeding over <24 hours), or A, ad lib (< or =4 hours nothing by mouth, with or without a single small feeding, then ad lib feedings). RESULTS: Of the 289 patients, 248 (80.5%) were boys. The average age of the patients was 5.64 weeks (range, 1 to 21 weeks). A total of 265 of 289 (92%) were full term. Thirty-nine of 289 (13.5%) had a family history positive for pyloric stenosis. A total of 104 of 289 (36%) were first-born infants, 89 of 289 (31%) were second born. The diagnosis of pyloric stenosis was made by a combination of physical examination findings and diagnostic image for most patients. An "olive" was palpated in 60.6% of the patients. Sixty percent (60.4%) of patients had an upper gastrointestinal series performed, and 42.5% were examined by ultrasonography. Overall, 53% of the patients had postoperative emesis. Only 3.5% had emesis that persisted greater than 48 hours after surgery. Patients fed ad lib after pyloromyotomy had slightly more emesis (2.2 A v. 1.2 R, and 0.7 I episodes, P = .002), but tolerated full feedings sooner than patients fed with a regimented or intermediate schedule. No patient required additional therapy or readmission after tolerating two consecutive full feedings, suggesting that this might be a suitable discharge criterion for most patients with HPS.

[Purulent pericarditis as an initial manifestation of esophageal carcinoma]. / Eitrige Perikarditis als Erstmanifestation eines Osophaguskarzinoms.

HISTORY AND ADMISSION FINDINGS: A 71-year old heavy smoker was admitted because of chest pain unrelated to physical activity, radiating into the left arm and neck as well as exertional dyspnoea and dizziness. Physical examination was unremarkable except for mild venous congestion over the upper part of the body. Myocardial infarction was excluded. A haemodynamically significant pericardial effusion developed a few days later and required emergency pericardiocentesis. INVESTIGATIONS: Laboratory tests indicated marked inflammatory disease. Echocardiography demonstrated the pericardial effusion. Needle aspiration revealed coagulase-negative staphylococcus and plant cells. Chest X-ray showed a pneumopericardium. Computed thoracic tomography suggested malignant tumour of the oesophagus with spread to the surrounding lymph nodes and pericardial fistula. Proximal endoscopy showed a highly malignant looking ulcer, 30 cm in diameter, in the anterior wall of the oesophagus with a central fistula. The endoscopic biopsy indicated a poorly differentiated non-cornified squamous cell carcinoma. TREATMENT AND COURSE: An uncovered self-expanding metal stent was placed into the fistula, whereupon the perimyocarditis quickly healed. When the patient was discharged he was able to take food by mouth and the signs of inflammation subsided. He died at home 6 weeks later. CONCLUSION: An oesophageal carcinoma with fistula should be included in the differential diagnosis of purulent pericardial effusion even in the absence of dysphagia. Implantation of a self-expanding metal stent into the fistula is the treatment of choice for palliation.

Stroke rehabilitation. 2. Co-morbidities and complications.

This self-directed learning module highlights new advances in the understanding of co-morbid conditions and medical complications of stroke. It is part of the chapter on stroke rehabilitation in the Self-Directed Physiatric Education Program for practitioners and trainees in physical medicine and rehabilitation. This article covers co-morbid conditions of stroke patients, including cardiovascular disease, diabetes, and sleep apnea. It reviews recent information on complications of stroke, including deep venous thrombosis, dysphagia and aspiration, hospital-acquired infections, depression, falls, spasticity, shoulder pain, and seizures. Treatment advances in diabetes, depression, and spasticity are highlighted. Recent information is presented regarding exercise guidelines for the stroke patient with cardiovascular disease, the relationship between stroke and sleep apnea, prophylaxis of deep venous thrombosis, the changing spectrum of hospital-acquired infections, malnutrition in stroke patients, the problem of falls during rehabilitation, the evaluation and management of poststroke shoulder pain, and the risk of seizures after stroke.

Stroke rehabilitation. 3. Rehabilitation management.

This self-directed learning module highlights new advances in the treatment of patients after stroke by means of a case study format. It is part of the chapter on stroke rehabilitation in the Self-Directed Physiatric Education Program for practitioners and trainees in physical medicine and rehabilitation. This article discusses both medical and rehabilitation issues that arise in the care of persons with strokes involving the right and left middle cerebral arteries and the vertebral artery. Cases were chosen to cover problems seen in both older and younger persons. Management of common sequelae that are typical of these stroke syndromes and identification of common co-morbidities are included.

Isolated fracture of the ventricular septum after blunt chest trauma.

Isolated rupture of of the ventricular septum after blunt chest trauma is a very rare traumatic affection. A 21-year-old man was admitted to our hospital because of blunt chest trauma and a forearm fracture. Initial echocardiography did not show any intracardiac or extracardiac pathologic lesions, but 12 hours later this examination was repeated because of the onset of a holosystolic murmur. An unusual traumatic rupture of the ventricular septum was demonstrated. The hemodynamically stable condition of the patient allowed surgical repair to be performed 3 months later.