The impact of FDG-PET/CT in the management of patients with vulvar and vaginal cancer.

OBJECTIVES: To evaluate the changes in prognostic impression and patient management following PET/CT in patients with vulvar and vaginal carcinoma; and to compare PET/CT findings with those of conventional imaging modalities. METHODS: We summarized prospectively and retrospectively collected data for 50 consecutive patients from our institution that enrolled in the National Oncologic PET Registry and underwent FDG-PET/CT for a suspected or known primary or recurrent vulvar/vaginal cancer. RESULTS: 54/83 (65%) studies included had a diagnosis of vulvar cancer, and the remaining 29/83 (35%), a diagnosis of vaginal cancer. Following FDG-PET/CT, the physician's prognostic impression changed in 51% of cases. A change in patient management, defined as a change to/from a non-interventional strategy (observation or additional imaging), to/from an interventional strategy (biopsy or treatment), was documented in 36% of studies. The electronic records demonstrated that 95% of the management strategies recorded in the physician questionnaires were implemented as planned. MRI and/or CT were performed within one month of the FDG-PET/CT in 20/83 (24%) and 28/83 (34%) cases, respectively. FDG-PET/CT detected nodes suspicious for metastases on 29/83 (35%) studies performed. MRI and CT detected positive nodes on 6 and 11 studies respectively. Distant metastases were identified in 10 cases imaged with FDG-PET and 5 cases that had additional conventional CT imaging. All suspicious lesions seen on CT were positively identified on PET/CT. In 4 cases, an abnormality identified on PET/CT, was not seen on diagnostic CT. CONCLUSIONS: FDG-PET/CT may play an important role in the management of vulvar and vaginal carcinoma.

Assessing skin pigmentation in epidemiological studies: the reliability of measurements under different conditions.

BACKGROUND/PURPOSE: Different devices are used for the non-invasive measurement of (constitutive) skin pigmentation in (epidemiological) studies. Reproducibility of measurements with the Chromameter (CM, model CR 300, Minolta, Osaka) and the Reflectometer (RM, Courage & Khazaka, Cologne) has not yet been examined in detail and was addressed in a set of four experiments and studies respectively. METHODS: Regarding the CM, the Y value of the Yxy CIE 1931 colour system was utilized, representing lightness in this colour space, while the RM measured reflectance at 660 nm with a small bandwidth of 20 nm. Both devices measure reflectance on a scale from 0 to 100%, however, in different wavelength ranges. Between 3 and 20 repetitions were performed on standard grey scales and different sets of human volunteers, including RM measurements in a large epidemiological field study. RESULTS: While the coefficient of variation (V) increases and the intraclass correlation coefficient decreases from controlled laboratory to field conditions, reproducibility remained in a range considered acceptable, if adequate study conditions were maintained. In a direct comparison on human skin, V of the RM was significantly smaller than that of the CM. CONCLUSION: Both devices can be used confidently in field studies; however, based on considerations of skin optics and in view of slightly lesser variability, the RM may be preferable.

Automatic texture-based analysis in ultrasound imaging of ovarian masses.

PURPOSE: To assess the diagnostic accuracy of a new automatic texture-based algorithm (ATBA) in ultrasound imaging of ovarian masses and to compare its performance to subjective assessment by examiners with different levels of ultrasound experience. MATERIALS AND METHODS: A total of 105 ultrasound images from three different groups of ovarian lesions (malignancies, functional cysts, and dermoid cysts) were evaluated using ATBA and by a total of 36 examiners with four different levels of experience (9 junior trainees, 8 senior trainees, 11 senior gynecologists, and 8 experts). Cohen's κ, Youden's indices, and the sensitivity and specificity of ATBA and of each observer were calculated for every subgroup of ovarian lesions. RESULTS: ATBA classified 78 of the 105 masses correctly (κ = 0.62) - results that were significantly better than those of the junior and senior trainees (p = 0.02 and p < 0.01), while differences from the group of level II examiners did not reach statistical significance (p = 0.27). The best diagnostic performance (κ = 0.70) was obtained by the group of expert level III ultrasonographers. The best classification rates overall, including both ATBA and subjective assessments, were achieved in the detection of functional cysts (Youden's indices from 0.73 to 0.85), while the poorest diagnostic performance was obtained for the classification of dermoid cysts (Youden's indices from 0.28 to 0.55). CONCLUSION: ATBA showed a significantly better diagnostic performance than observers with low or medium levels of experience, emphasizing its potential value for training purposes and in providing additional diagnostic assistance for inexperienced observers.

Motor imagery in stroke patients, or plegic patients with spinal cord or peripheral diseases.

OBJECTIVES: When motor imagery (MI) is impaired in stroke patients, it is not clear, whether this is caused by the central lesion with a disruption of networks or this may be due to inactivity/lack of practice following hemiparesis. To answer this question, we investigated MI in two groups of patients: stroke patients and patients with no central lesion, who suffered high-grade tetraparesis caused by myopathy or spinal muscular atrophy. MATERIALS AND METHODS: The first study measured MI in 31 sub-acute and chronic stroke patients with hand paresis. We used self-assessment questionnaires [Kinaesthetic and Visual Imagery Questionnaire (KVIQ), the Vividness of Motor Imagery Questionnaire (VMIQ)] as well as a new chronometric test (mental version and normal/physical version of Box and Block Test). The second study assessed MI in 10 patients without a central lesion, but with severe tetraparesis of peripheral origin. They were incapable of performing the requested task physically. RESULTS: MI in patients was better (i) for the third-person (VMIQ(3.P) ) compared to the first-person perspective (VMIQ(1.P) ), (ii) in patients without sensory impairment compared to those with impaired proprioception, (iii) in patients with light paresis compared to severe paresis and (iv) for the non-affected than the affected hand (KVIQ-10). Patients with severe tetraparesis were able to imagine another person's knee bends, but were not capable of imagining themselves performing knee bends. CONCLUSIONS: MI may be hampered on the affected side in severely paretic patients, particularly in the presence of impaired proprioception. Remarkably, the second study illustrates that motor experiences shape MI. This confirms the close relationship between MI and movement execution. The study advocates the careful use of test batteries for assessment of MI when investigating mental training in clinical trials. Not all patients might benefit to the same extent from MI training. This is possibly contingent on intact proprioception and preserved MI.

Droplet microarrays for cell culture: effect of surface properties and nanoliter culture volume on global transcriptomic landscape.

The development of novel chemically developed and physically defined surfaces and environments for cell culture and screening is important for various biological applications. The Droplet microarray (DMA) platform based on hydrophilic-superhydrophobic patterning enables high-throughput cellular screening in nanoliter volumes and on various biocompatible surfaces. Here we performed phenotypic and transcriptomic analysis of HeLa-CCL2 cells cultured on DMA, with a goal to analyze cellular response on different surfaces and culture volumes down to 3 nL, compared with conventional cell culture platforms. Our results indicate that cells cultured on four tested substrates: nanostructured nonpolymer, rough and smooth variants of poly(2-hydroxyethyl methacrylate-co-ethylene dimethacrylate) polymer and poly(thioether) dendrimer are compatible with cells grown in Petri dish. Cells cultured on nanostructured nonpolymer coating exhibited the closet transcriptomic resemblance to that of cells grown in Petri dish. Analysis of cells cultured in 100, 9, and 3 nL media droplets on DMA indicated that all but cells grown in 3 nL volumes had unperturbed viability with minimal alterations in the transcriptome compared with 96-well plate. Our findings demonstrate the applicability of DMA for cell-based assays and highlight the possibility of establishing regular cell culture on various biomaterial-coated substrates and in nanoliter volumes, along with routinely used cell culture platforms.

Increase in salicylic Acid at the onset of systemic acquired resistance in cucumber.

In an effort to identify the signal compound that mediates systemic acquired resistance (SAR), changes in the content of phloem sap were monitored in cucumber plants inoculated with either tobacco necrosis virus or the fungal pathogen Colletotrichum lagenarium. The concentration of a fluorescent metabolite was observed to increase transiently after inoculation, with a peak reached before SAR was detected. The compound was purified and identified by gas chromatography-mass spectrometry as salicylic acid, a known exogenous inducer of resistance. The data suggest that salicylic acid could function as the endogenous signal in the transmission of SAR in cucumber.

Solid-phase combinatorial synthesis using microarrays of microcompartments with light-induced on-chip cell screening.

The process of drug discovery includes individual synthesis and characterization of drug candidates, followed by a biological screening, which is separated from synthesis in space and time. This approach suffers from low throughput and associated high costs, which in turn lead to inefficiency in the field of drug discovery. Here, we present a miniaturized platform combining combinatorial solid-phase synthesis with high-throughput cell screenings. The method is based on the formation of nanoporous poly(2-hydroxyethyl methacrylate-co-ethylene dimethacrylate) layers patterned with hydrophilic spots separated from each other by superhydrophobic liquid-impermeable barriers. The porous polymer inside the hydrophilic spots is used as a support to conduct solid-phase synthesis. The hydrophilic spots can be then filled with droplets containing either reagents for synthesis or live cells. Upon irradiation with UV light, products of solid-phase synthesis are released from the porous polymer because of the photo-cleavable linkers used and diffuse into separate droplets. The light-induced release of the products allows the control of the release spatially, temporally, and quantitatively. To demonstrate the versatility and usability of the platform for various cell lines, we have successfully implemented peptide synthesis to create an exemplary chemical library and demonstrated high cell viability after the UV-triggered small-molecule release.

Acute effects of hemodialysis on salivary flow rate and composition.

AIMS: To evaluate acute effects of hemodialysis (HD) on the salivary flow rate, pH and biochemical composition before, during and after completion of a dialysis session. MATERIAL AND METHODS: Unstimulated whole saliva (UWS) and chewing-stimulated whole saliva (CH-SWS) were collected in 94 HD patients. Salivary flow rate, pH, concentrations of total protein, albumin, cystatin C, secretory immunoglobulin A (S-IgA) and of sodium, potassium and urea were measured. RESULTS: HD had an acute stimulating effect on the salivary flow rate (UWSbefore = 0.30+/-0.22 ml/min, UWSduring = 0.39+/-0.25 ml/min, p < 0.005). The mean pH of UWS showed a small but significant increase during HD mainly due to an increased watery secretion from the salivary glands. The salivary biochemical constituents changed markedly, but no significant difference in output was found. The electrolyte concentration did not change significantly during dialysis. The level of urea in CH-SWS declined to 40% (Ureabefore = 25.+/-6.4 mmol/l, Ureaduring = 15.3+/-4.5 mmol/1). CONCLUSIONS: This study shows that HD has significant acute effects on both salivary secretion rate and protein concentrations in saliva. We conclude that the observed changes in salivary concentrations and proteins are mainly due to an increased watery secretion from the salivary glands.

[On the relation between binaural difference potentials and directional hearing]. / Zur Beziehung zwischen den binauralen Differenzpotentialen und dem Richtungshörvermögen.

BACKGROUND: Central auditory processing disorders (CAPD) are associated with reduced discriminatory abilities of the auditory system. One of these abilities is directional hearing, which is based on the evaluation of interaural signal differences. Since these differences affect also the binaural difference potentials (BDP), these derived evoked potentials could be suitable for the objective detection of disabilities in acoustic localization. METHOD: Auditory brainstem responses (ABR) evoked by monaural and binaural stimulation were recorded in 32 adult normal-hearing volunteers at stimulus levels between 10 and 80 dB nHL and the BDP were derived. Additionally, a test of directional hearing was performed and evaluated. RESULTS: BDP are detectable at all stimulus levels without difficulties, with acceptable examination times and with satisfactory reliability in a routine clinical environment. The electrodes can be positioned at the mastoid (A1 and A2) and vertex (Cz) as for conventional ABR recording. Normal ranges are given for latency and amplitude as well as for their lateral differences. CONCLUSION: The spectrum in directional hearing ability as covered by normal-hearing subjects is not mirrored in the parameters of their BDP. Nevertheless, it cannot be ruled out that a real impairment of directional hearing goes along with significantly altered BDP.

[Enuresis in childhood]. / Serie Kindersprechstunde, Teil 2: Enuresis. "Mein Kind ist Bettnässer"!

In children with nocturnal bedwetting, the basic diagnostic evaluation to differentiate between monosymptomatic enuresis and organic or functional urinary incontinence is mandatory. When the diagnosis of monosymptomatic enuresis is set, a stepped therapeutic program is available, in which alarm/behavior therapy has a central role. Drug therapy of monosymptomatic enuresis in childhood is an established option and is reserved for certain indications.

Baby food exchanges and feeding the diabetic infant.

Because of the dangers of hypoglycemia to the developing brain, the need to develop a lifelong positive attitude toward an eating pattern, the inherent communication difficulties, and the spontaneity of the very young, the diabetic infant presents a particular challenge to medical personnel. Baby and toddler foods in jar measurements and formula have been translated into the American Diabetes Association exchanges to help in teaching families with diabetic infants the effects of various foods on the infant's diabetes. The exchanges are taught as tools in maintaining metabolic balance rather than as a fixed diet. Caloric level is planned on the basis of diet history and the infant's current growth status. Flexibility of pattern and attitude is emphasized to minimize conflict over eating and to allow normal spontaneous activity without jeopardizing health.

Hot and cold mate drinking and esophageal cancer in Paraguay.

A hospital-based case-control study, including 131 cases of esophageal cancer and 381 controls, was carried out in Paraguay to investigate the role of hot and cold mate drinking in esophageal cancer risk. Detailed information on mate drinking and on tobacco smoking, alcohol consumption, and dietary habits was obtained by interview. Amount and duration of cold or hot mate drinking were not associated with esophageal cancer risk. However, temperature at which mate was drunk was significantly associated with risk. As compared to drinkers of warm or hot mate, drinkers of very hot mate had an increased risk for esophageal cancer even after adjusting for the strong effects of alcohol and tobacco consumption (adjusted odds ratio = 2.4; 95% confidence interval = 1.3-4.3). This effect seemed to be mainly due to the temperature at which mate cocido (one of the two ways in which hot mate is prepared) was drunk (odds ratio = 6.5; 95% confidence interval = 3.2-12.2). As expected, very strong dose-response associations were found for alcohol consumption and cigarette smoking. After correcting for these and the consumption of other food groups, diets rich in fats and red meats, especially beef, were associated with esophageal cancer risk. In conclusion, the findings from this study suggest that cold mate drinking does not increase the risk of esophageal cancer. This study identifies the very hot temperature at which mate is drunk, and not the amount or the duration, as an important risk factor for esophageal cancer in this population. Alcohol drinking and tobacco smoking remain, nevertheless, the main risk factors for esophageal cancer in Paraguay.

Humic acid reduction by propionibacterium freudenreichii and other fermenting bacteria

Iron-reducing bacteria have been reported to reduce humic acids and low-molecular-weight quinones with electrons from acetate or hydrogen oxidation. Due to the rapid chemical reaction of amorphous ferric iron with the reduced reaction products, humic acids and low-molecular-weight redox mediators may play an important role in biological iron reduction. Since many anaerobic bacteria that are not able to reduce amorphous ferric iron directly are known to transfer electrons to other external acceptors, such as ferricyanide, 2,6-anthraquinone disulfonate (AQDS), or molecular oxygen, we tested several physiologically different species of fermenting bacteria to determine their abilities to reduce humic acids. Propionibacterium freudenreichii, Lactococcus lactis, and Enterococcus cecorum all shifted their fermentation patterns towards more oxidized products when humic acids were present; P. freudenreichii even oxidized propionate to acetate under these conditions. When amorphous ferric iron was added to reoxidize the electron acceptor, humic acids were found to be equally effective when they were added in substoichiometric amounts. These findings indicate that in addition to iron-reducing bacteria, fermenting bacteria are also capable of channeling electrons from anaerobic oxidations via humic acids towards iron reduction. This information needs to be considered in future studies of electron flow in soils and sediments.

The sap47 gene of Drosophila melanogaster codes for a novel conserved neuronal protein associated with synaptic terminals.

Proteins expressed specifically in neurons and transported to synaptic terminals are likely to constitute important molecular elements of nervous system function. In an effort to characterize synapse-associated proteins (SAPs) of Drosophila, we have isolated from a hybridoma library several monoclonal antibodies (MABs) that selectively stain synaptic terminals in immunohistochemical preparations. MAB nc46 binds to most but not all synaptic terminals of the Drosophila nervous system, it also recognizes a protein with homologous distribution in other dipteran flies and binds to large parts of fish CNS. In Western blots the antibody labels a Drosophila brain protein of 47 kDa and cross-reacts with brain proteins from several species including insects, fish, mouse and man. From these data we conclude that the corresponding gene has been conserved in evolution at least among diptera. Using MAB nc46 and expression cloning we have identified the 'sap47' gene coding for the 'synapse-associated protein of 47 kDa' of Drosophila melanogaster. Sequence analysis of genomic and cDNA clones reveals the intron-exon structure of the gene and characterizes the complete open reading frames of two alternatively spliced transcripts. The sap47 gene is located in 89A8-B3 on chromosome 3R and codes for two almost identical inferred polypeptides of 347 and 351 amino acids with no significant sequence homology to known proteins.

Antioxidants, Helicobacter pylori and stomach cancer in Venezuela.

A randomized chemoprevention trial on precancerous lesions of the stomach is being conducted in Tachira State, Venezuela. The aims of the study are to evaluate the efficacy of vitamin supplementation in preventing the progression rate of precancerous lesions. Here we report on the pilot phase of the study in which two antioxidant preparations were evaluated on their ability to raise antioxidant levels in plasma and in gastric juice. The study aimed also to determine the antibiotic sensitivity profiles of Helicobacter pylori isolates prevalent in the area. Forty-three subjects with precancerous lesions (chronic gastritis, chronic atrophic gastritis, intestinal metaplasia and dysplasia) of the stomach were randomized to one of two antioxidant treatments. Treatment 1 (250 mg of standard vitamin C, 200 mg of vitamin E and 6 mg of beta-carotene three times a day) or treatment 2 (150 mg of standard vitamin C, 500 mg of slow release vitamin C, 75 mg of vitamin E and 15 mg of beta-carotene once a day) for 7 days. Blood levels of total vitamin C, beta-carotene and alpha-tocopherol and gastric juice levels of ascorbic acid and total vitamin C were measured before and after treatment on day 8. Both treatments increased the plasma levels of total vitamin C, beta-carotene and alpha-tocopherol/cholesterol but not those of ascorbic acid or total vitamin C in gastric juice. Treatment 1 was the best choice and resulted in a greater increase in the plasma levels of beta-carotene and alpha-tocopherol. H. pylori was cultured from 90% of the gastric biopsies; 35 isolates were identified which were highly resistant to metronidazole, a front-line antibiotic recommended against H. pylori in other settings.

Immunochemical analysis of high molecular-weight human salivary mucins (MG1) using monoclonal antibodies.

Using four Mabs with different specificities for salivary mucins, an ELISA has been developed in which human whole saliva, glandular salivas, salivary protein fractions and purified, high molecular-weight, mucin fractions (MG1) isolated from human submandibular and sublingual glandular tissues have been immunochemically analysed. All four Mabs reacted with MG1s. Three of them reacted with the purified, low molecular-weight salivary mucins (MG2). None was reactive with parotid saliva. MG1 preparations isolated from submandibular and sublingual glandular tissues of one and the same individual displayed different patterns of reactivity with these Mabs, indicating that they differ immunochemically. Analysis of the MG1s in salivas derived from individual salivary glands showed differences in immunochemical composition. These results indicate that the MG1 fraction in human whole saliva consists of several immunochemically different species.

Hertel exophthalmometry versus computed tomography and optical 3D imaging for the determination of the globe position in zygomatic fractures.

It has been the aim of the present study, to introduce the combination of computed tomography and optical 3D imaging to exophthalmometry and to compare the resulting data to the classic Hertel method. Twenty patients without orbital pathology and 12 patients were included in the study, who were subjected to a preoperative computed tomography. Optical 3D images of the facial surface were assessed and Hertel exophthalmometry was carried out to determine protrusion. In patients with zygomatic fractures the assessment of optical 3D images and Hertel values was repeated 5 days after surgery. Preoperative axial CT slices and postoperative optical contours through the globes were superimposed and the change in protrusion was determined. The protrusion values assessed either by CT, Hertel exophthalmometry or optical 3D imaging for patients without orbital pathology did not show any statistically significant differences between each other. For zygomatic fractures, Hertel exophthalmometry revealed more pronounced protrusion data in four of five cases of a posterolaterally dislocated lateral orbital rim and a higher degree of enophthalmos in cases without dislocation of the lateral orbital rim than it could be proved in the CT slices. The differences between optical measurements and CT data were minimal in patients with zygomatic fractures. The combination of computed tomography as baseline measurement and optical 3D imaging for the follow-up examinations reveal more realistic data in cases of zygomatic fractures than Hertel measurements and should be preferred.

Do site-specific radiocarbon measurements reflect localized distributions of 14C in biota inhabiting a wetland with point contamination sources?

Duke Swamp is a wetland ecosystem that receives (14)C via a groundwater pathway originating from a waste management area on Atomic Energy Canada Limited's Chalk River Laboratories site. This groundwater reaches the surface of the swamp, resulting in relatively high (14)C levels over an area of 146 m(2). The objective of this study was to quantify (14)C concentrations in flora and fauna inhabiting areas of Duke Swamp over the gradient of (14)C activity concentrations in moss to determine whether (14)C specific activities in receptor biota reflect the localized nature of the groundwater source in the swamp. Representative receptor plants and animals, and corresponding air and soil samples were collected at six sites in Duke Swamp with (14)C specific activities in air that ranged from 1140 to 45,900 Bq/kg C. In general, it was found that specific activities of (14)C in biota tissues reflected those measured in environmental media collected from the same sampling site. The findings demonstrate that mosses could be used in monitoring programs to ensure protection of biota in areas with elevated (14)C, negating the need to capture and euthanize higher organisms.

Risk factors and containment of respiratory syncytial virus outbreak in a hematology and transplant unit.

Respiratory syncytial virus (RSV) usually causes self-limiting upper respiratory tract infections, but can be associated with severe lower respiratory tract infection disease (LRTID) in infants and in patients with hematologic malignancies. We have analyzed the risk factors and the measures for containment within an outbreak of nosocomial RSV infections in a hematology and SCT unit. A total of 56 patients were affected (53 RSV-A and 3 RSV-B) including 32 transplant patients (16 allogeneic and 16 autologous). Forty (71%) of the 56 patients suffered from LRTID and 14 (35%) of the patients with LRTID subsequently died. However, because of concomitant infections with fungal and bacterial pathogens, the impact of RSV on the fatal outcome was difficult to assess. Multivariate analysis showed that low levels of IgG were significantly associated with fatal outcome (P=0.007), treatment with oral ribavirin represented a protective factor (P=0.02). An extremely protracted viral shedding was observed in this cohort of patients (median=30.5 days, range: 1-162 days), especially pronounced in patients after allogeneic transplantation (P=0.002). Implementation of rigorous isolation and barrier measures, although challenged by long-term viral carriers, was effective in containment of the outbreak.

(18)F-FDG-PET/CT in evaluating response to therapy in solid tumors: where we are and where we can go.

In the past, enormous public and private investments have been made to reduce cancer incidence and mortality. Despite some improvements over the last 10 years, the overall outcome of the "war on cancer" has been disappointing. Among the reasons for this limited success is our inability to determine, whether the therapeutic target is present, and whether the target is reached by the drug. A further important issue is our limited ability to correctly assess response to treatment early after start of therapy which would allow for more individualized treatment approaches. PET and PET/CT with the glucose analogue 2'-[(18)F]-fluoro-2'-deoxy-D-glucose (FDG) are increasingly used to assess response to therapy in patients, and a converging large body of evidence is emerging that suggests that changes in glucose utilization during therapy can be used to predict clinical outcome. In this article we provide an overview of the utility of (18)F-FDG PET/CT imaging for early monitoring of cancer therapy and address current and future challenges for its more widespread adoption. First, we discuss general requirements that any imaging modality must meet to provide valid and valuable treatment response assessment. We will then review the strengths and limitations of CT (RECIST) and PET based response criteria. Finally, we will examine the role of FDG-PET/(CT) imaging for response assessments in solid tumors.