Antimicrobial therapy of febrile complications after high-dose chemo-/radiotherapy and autologous hematopoietic stem cell transplantation--guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Oncology (DGHO)

Infectious complications occur in 60-100% of patients following high-dose chemotherapy (HDC) and autologous hematopoietic stem cell transplantation (HSCT), and are commonly caused by Gram-negative aerobic bacteria (such as Pseudomonas aeruginosa and enterobacteriacea e) and Gram-positive cocci (such as enterococci, streptococci and staphylococci), which should be covered by empiric first-line antibiotic therapy. Less frequently, infections are caused by fungi and anaerobic bacteria, and initial therapy does not necessarily have to cover coagulase-negative staphylococci, oxacillin-resistant S. aureus (MRSA), anaerobic bacteria and fungi. Patients who already receive antibiotics and develop pulmonary infiltrates should immediately be treated with systemic antifungals. Patients with fever and diarrhea or other signs and symptoms of gastrointestinal or perianal infection should be treated with antibiotics covering anaerobic bacteria and enterococci. Clinically stable patients with skin infections or central venous catheter-related infections can be treated with standard empiric antibiotic therapy including a beta-lactam active against Pseudomonas aeruginosa with or without an aminoglycoside, and should only receive glycopeptides if they do not respond to first-line therapy within 72 hours, become clinically unstable, have severe mucositis, or when resistance against the empiric antibiotics is demonstrated. Recombinant hematopoietic growth factors should not be added routinely but may be considered in life-threatening situations such as invasive pulmonary mycoses or sepsis.     

Monoclonal and biclonal gammopathy in two patients infected with<Emphasis Type="Italic"> Bartonella henselae</Emphasis>

Two immunocompetent patients with cat-scratch disease due to infection with Bartonella henselae developed monoclonal and biclonal gammopathy. Neither patient had evidence of any other known cause of plasma cell dyscrasia, and antibiotic eradication of Bartonella henselae infection resulted in the prompt disappearance of the gammopathy. Hence, cat-scratch disease should be added to the list of possible underlying disorders in individuals presenting with monoclonal and biclonal gammopathy.     

Performance of basic manipulation and intracorporeal suturing tasks in a robotic surgical system: single- versus dual-monitor views

Background  Technical advances in the application of laparoscopic and robotic surgical systems have improved platform usability. The authors hypothesized that using two monitors instead of one would lead to faster performance with fewer errors. Methods  All tasks were performed using a surgical robot in a training box. One of the monitors was a standard camera with two preset zoom levels (zoomed in and zoomed out, single-monitor condition). The second monitor provided a static panoramic view of the whole surgical field. The standard camera was static at the zoomed-in level for the dual-monitor condition of the study. The study had two groups of participants: 4 surgeons proficient in both robotic and advanced laparoscopic skills and 10 lay persons (nonsurgeons) who were given adequate time to train and familiarize themselves with the equipment. Running a 50-cm rope was the basic task. Advanced tasks included running a suture through predetermined points and intracorporeal knot tying with 3–0 silk. Trial completion times and errors, categorized into three groups (orientation, precision, and task), were recorded. Results  The trial completion times for all the tasks, basic and advanced, in the two groups were not significantly different. Fewer orientation errors occurred in the nonsurgeon group during knot tying (p = 0.03) and in both groups during suturing (p = 0.0002) in the dual-monitor arm of the study. Differences in precision and task error were not significant. Conclusions  Using two camera views helps both surgeons and lay persons perform complex tasks with fewer errors. These results may be due to better awareness of the surgical field with regard to the location of the instruments, leading to better field orientation. This display setup has potential for use in complex minimally invasive surgeries such as esophagectomy and gastric bypass. This technique also would be applicable to open microsurgery. Presented at the 2008 SAGES meeting.     

IVF过程受精失败的预测

在发明和常规应用卵胞浆内单精子注射（ICSI）之前,十多年的临床体外受精（IVF）治疗实践中,受精率低下很常见,大约有20％～35％的IVF患者受精率很低（〈35％的卵子受精）和受精完全失败（所有卵子都不受精）。虽然受精失败与精子或卵子的质量有关,但相当一部分患者受精失败与精液质量或精子功能低下有很密切相关性。最常见的是严重的少精,弱精和畸形精子症患者。     

Proof-of-concept study on the suitability of 13C-urea as a marker substance for assessment of in vivo behaviour of oral colon-targeted dosage forms

Background and purpose:

¹³C-urea may be a suitable marker to assess the in vivo fate of colon-targeted dosage forms given by mouth. We postulated that release in the colon (urease-rich segment) of ¹³C-urea from colon-targeted capsules would lead to fermentation of ¹³C-urea by bacterial ureases into ¹³CO₂. Subsequent absorption into the blood and circulation would lead to detectable ¹³C (as ¹³CO₂) in breath. If, however, release of ¹³C-urea occurred in the small intestine (urease-poor segment), we expected detectable ¹³C (as ¹³C-urea) in blood but no breath ¹³C (as ¹³CO₂). The differential kinetics of ¹³C-urea could thus potentially describe both release kinetics and indicate the gastrointestinal segment of release.

Experimental approach:

The in vivo study consisted of three experiments, during which the same group of four volunteers participated.

Key results:

The kinetic model was internally valid. The appearance of ¹³C-in breath CO₂ (F_fermented) and the appearance of ¹³C in blood as ¹³C-urea (F_{not fermented}) show a high inverse correlation (Pearson''s r=−0.981, P= 0.06). The total recovery of ¹³C (F_fermented+F_{not fermented}) averaged 99%, indicating complete recovery of the administered ¹³C via breath and blood. ¹³CO₂ exhalation was observed in all subjects. This indicates that ¹³C-urea was available in urease-rich segments, such as the caecum or colon.

Conclusions and implications:

In this proof-of-concept study, ¹³C-urea was able to provide information on both the release kinetics of a colon-targeted oral dosage form and the gastrointestinal segment where it was released.     

Raman spectroscopy detects and distinguishes neuroblastoma and related tissues in fresh and (banked) frozen specimens

Background

Raman spectroscopy has been shown to accurately distinguish different neural crest-derived pediatric tumors. This study tests the ability of Raman spectroscopy to accurately identify cryopreserved tissue specimens using a classification algorithm designed from fresh tumor data and vice versa.

Methods

Fresh specimens of neuroblastoma and other pediatric neural crest tumors were analyzed with Raman spectroscopy. After analysis, the specimens were stored at −80°C. At a later date, the specimens were thawed and reanalyzed by Raman spectroscopy. A computer algorithm was used to classify the spectra from the frozen tissue against a computer model built on the fresh tissue data. This classification process was then reversed, testing fresh spectra against a model built from frozen data.

Results

We collected 1114 spectra (862 fresh and 252 frozen) from 62 tissue samples, including 8 normal adrenal glands, 29 neuroblastomas, 14 ganglioneuromas, 8 nerve sheath tumors, and 3 pheochromocytomas. At the tissue level, frozen neuroblastoma, ganglioneuroma, nerve sheath tumor, and pheochromocytoma were distinguished from normal adrenal tissue with 100% sensitivity and specificity. Fresh tissue had the same results except for the misclassification of one specimen of nerve sheath tumor.

Conclusions

The representative spectra show a high correlation between fresh and frozen tissue, and a clear difference between pathologic conditions. Spectra from frozen tissue can be accurately classified against spectra from fresh tissue and vice versa. This modality makes it possible to determine in a few minutes a result that often takes 12 to 36 hours for tissue processing and consideration by a trained pathologist to achieve.     

The Enduro motorcyclist's wrist and other overuse injuries in competitive Enduro motorcyclists: a prospective study

According to public opinion, Enduro motorcycling is a dangerous sport. Little is known about overuse injuries in connection with this sport. The study consisted of two phases. Phase 1 was planned as a prospective feasibility study for phase 2. The latter was initiated as a prospective investigation, comprising a random sample of the participants of phase 1. Enduro motorcyclists were interviewed with a prepared questionnaire. Clinical examinations were performed immediately before, and after, a major Enduro race, including pain assessment in the hand/wrist and the forearm using the visual analog scale. The occurrence of Raynaud's syndrome carpal tunnel syndrome (CTS), and loss of grip strength in the forearm muscles were recorded in detail. Phase 1 showed that the predominant overused anatomical regions were the hand/wrist and forearms. Nearly 50% of all the riders complained of pain or paresthetic sensations. A significant increase in pain was registered after the race. After the second run 32.28% of all riders had CTS in the left hand and 43.31% in the right hand. More than one‐half of the athletes complained of overuse injuries. Transient CTS is an overuse injury closely related to sports.     

Molecular Typing of Coagulase-Negative Staphylococcal Blood and Skin Culture Isolates to Differentiate Between Bacteremia and Contamination

In order to determine whether a blood culture positive for coagulase-negative staphylococci (CNS) represents bacteremia or contamination, a prospective study was conducted using molecular typing to analyze CNS blood culture isolates and corresponding CNS skin isolates collected after skin disinfection from 431 subjects. CNS bacteremia was not found in any of the 301 subjects not suspected of having bacteremia. In 130 patients suspected of having bacteremia, the rate of actual CNS bacteremia was 6%. The overall rate of CNS blood culture contamination was 1%. Chart analysis showed good agreement between our microbiological definitions of bacteremia and the clinical definitions previously published. Bacteremia and contamination can be differentiated using pulsed-field gel electrophoresis and molecular typing of CNS isolates obtained from cultures of blood and corresponding skin samples.     

Mechanism of action of dietary chemoprotective agents in rat liver: induction of phase I and II drug metabolizing enzymes and aflatoxin B1 metabolism

A range of potential chemoprotective agents, most of them natural dietary constituents, has been examined for ability to modulate both phase I (cytochrome P450 1A1, 1A2, 2B1/2, 2C11, 2E1, 3A, 4A) and phase II drug metabolizing enzymes (glutathione S-transferases, in particular subunits Yc2 and P, aflatoxin B1-aldehyde reductase and quinone reductase) in rat liver. In addition to assays of total enzyme activity and Western blots for individual isozymes, the ability of microsomes to metabolize aflatoxin B1, and of cytosols to conjugate aflatoxin B1 (AFB1)-epoxide to GSH and to produce AFB1-dialcohol, were measured. Induction of gamma-glutamyl transpeptidase activity was examined by histochemistry. Differing patterns of induction were observed, reflecting differences in the control of expression of the individual enzymes studied. Of the compounds examined, butylated hydroxytoluene, ethoxyquin, indole-3-carbinol and phenethyl isothiocyanate were the most potent bifunctional agents (inducing both phase I and II activities). Oltipraz, while only weakly inducing CYP1A2 and 2B1/2, was a potent inducer of phase II enzymes. Caffeic acid, garlic oil, sinigrin and propyl gallate all showed some ability to induce phase II enzymes. 4-Methyl catechol, alpha-tocopherol and red wine decreased certain phase I enzyme activities, while inducing total GST activity. Butylated hydroxytoluene, ethoxyquin, garlic oil and indole-3-carbinol induced gamma glutamyltranspeptidase in periportal hepatocytes. Particularly because of their ability to induce the detoxifying activities of glutathione S-transferase Yc2 and aldehyde reductase, butylated hydroxytoluene, ethoxyquin, indole-3-carbinol, oltipraz, phenethyl isothiocyanate and sinigrin will be effective blocking agents in rodents, if administered prior to AFB1. While these studies indicate the relative contributions of phase I and II metabolism in the overall protective effect in rat, care should be taken that a similar balance is achieved in man, and that relevant enzymes or iso forms are induced.