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Dosimeter gel and MR imaging for verification of calculated dose distributions in clinical radiation therapy.

A dosimeter gel, based on an agarose gel infused with a ferrous sulphate solution and evaluated in a magnetic resonance scanner, was used for complete verification of calculated dose distributions. Two standard treatment procedures, treatment of cancer in the urinary bladder and treatment of breast cancer after modified radical mastectomy, were examined using pixel-by-pixel and dose volume histogram comparison. The dose distributions calculated with the dose planning system was in very good agreement with the measured ones. However, in the case of the more complicated breast cancer treatment, some discrepancies were found, mainly at the beam abutment region. This may be explained by field displacements errors and by a small limitation of the dose planning utilising small electron beams in this region. The dosimeter gel system have proven to be a useful tool for dosimetry in clinical radiation therapy applications.

Breast Neoplasms↗

Brain- and heart-type fatty acid-binding proteins in the brain: tissue distribution and clinical utility.

BACKGROUND: Detection of brain injury by serum markers is not a standard procedure in clinical practice, although several proteins, such as S100B, neuron-specific enolase (NSE), myelin basic protein, and glial fibrillary acidic protein, show promising results. We investigated the tissue distribution of brain- and heart-type fatty acid-binding proteins (B-FABP and H-FABP) in segments of the human brain and the potential of either protein to serve as plasma marker for diagnosis of brain injury. METHODS: B-FABP and H-FABP were measured immunochemically in autopsy samples of the brain (n = 6) and in serum samples from (a) patients with mild traumatic brain injury (MTBI; n = 130) and (b) depressed patients undergoing bilateral electroconvulsive therapy (ECT; n = 14). The protein markers S100B and NSE were measured for comparison. Reference values of B-FABP and H-FABP were established in healthy individuals (n = 92). RESULTS: The frontal, temporal, and occipital lobes, the striatum, the pons, and the cerebellum had different tissue concentrations of B-FABP and of H-FABP. B-FABP ranged from 0.8 microg/g wet weight in striatum tissue to 3.1 microg/g in frontal lobe. H-FABP was markedly higher, ranging from 16.2 microg/g wet weight in cerebellum tissue to 39.5 microg/g in pons. No B-FABP was detected in serum from healthy donors. H-FABP serum reference value was 6 microg/L. In the MTBI study, serum B-FABP was increased in 68% and H-FABP in 70% of patients compared with S100B (increased in 45%) and NSE (increased in 51% of patients). In ECT, serum B-FABP was increased in 6% of all samples (2 of 14 patients), whereas H-FABP was above its upper reference limit (6 microg/L) in 17% of all samples (8 of 14 patients), and S100B was above its upper reference limit (0.3 microg/L) in 0.4% of all samples. CONCLUSIONS: B-FABP and H-FABP patterns differ among brain tissues, with the highest concentrations in the frontal lobe and pons, respectively. However, in each part of the brain, the H-FABP concentration was at least 10 times higher than that of B-FABP. Patient studies indicate that B-FABP and H-FABP are more sensitive markers for minor brain injury than the currently used markers S100B and NSE.

Adult↗

Privacy-Preserving Linkage of Distributed Biological, Clinical, and Imaging Data Supporting Artificial Intelligence in Pediatric Oncology.

BACKGROUND: Cancer remains the leading cause of disease-related mortality in children over the age of one in Europe, with over 35,000 new pediatric cases and more than 6,000 deaths annually. Due to the rarity of pediatric cancers, clinical trial protocols often substitute for formal treatment guidelines, resulting in many children being enrolled in multiple trials, with biological samples and genomic data stored in various biobanks. Data collection in pediatric oncology is challenging, with sparse data acquired over extended periods, underscoring the need for optimal utilization of all available information through linked, privacy-preserving datasets. METHODS: Here, we report the development of a distributed, privacy-preserving data infrastructure for the PRIMAGE project, a European initiative aimed at supporting artificial intelligence (AI)-driven image analysis for pediatric cancer prognostics. The infrastructure leverages the European Patient Identity (EUPID) Services for Privacy-Preserving Record Linkage, enabling pseudonymized data integration across clinical, biological, and imaging sources. The system incorporates EUPID's hashing and phonetic matching protocols to pseudonymize patient identifiers and link distributed datasets, facilitating secondary data use in compliance with the General Data Protection Regulation. RESULTS: Data from over 700 neuroblastoma patients from European trials and hospitals were linked and uploaded to the PRIMAGE platform, where AI models predict clinical outcomes. CONCLUSION: This infrastructure successfully facilitated AI model development, advancing pediatric oncology research, and offering a scalable framework for future European health data initiatives, such as the European Health Data Space.

Journal Article↗

[Anatomical investigation of arterial distribution and clinical application of selective angiography of the shoulder joint].

The purpose of this paper is to apply selective angiography to the shoulder joint based on anatomical quantitative study. Prior to the selective angiography, I made the arterial casts of adult cadavers (30 joints) to investigate the vascular distribution of the rotator cuff, and the arterial specimen of fetus cadavers (60 joints) using a modification of Teichmann's technique with cold injection medium to observe the types of origin of the main arteries roentgenographically. Results of these anatomical studies showed the rotator cuff to have 4 main arteries, and each tendon of the rotator cuff to have 2 or more arteries from the scapular side and the humeral side, forming a vascular network on the tendon. The critical zone of the vascular network was in the subacromial part of the rotator cuff where the selective angiogram showed a variety of abnormal vasculature in clinical cases with lesions at the supraspinatus tendon.

Adult↗

Intestinal-type and liver-type fatty acid-binding protein in the intestine. Tissue distribution and clinical utility.

OBJECTIVES: Intestinal-type fatty acid-binding protein (I-FABP) has been proposed as plasma marker for the detection of acute intestinal injury. However, intestinal mucosa also expresses liver-type FABP (L-FABP). We have investigated the tissue distribution of I-FABP and L-FABP in segments of the human intestine along the duodenal to colonal axis and the potential of both proteins to serve as plasma marker for the diagnosis of intestinal injury. DESIGN AND METHODS: I-FABP and L-FABP were measured with specific immunoassays in autopsy samples of the intestine (duodenum, jejunum, ileum and colon) of 23 subjects and in plasma samples from patients (n = 51) with intestinal and/or hepatic disease. Plasma reference values were established in normal healthy individuals (n = 92). RESULTS: The I-FABP tissue contents in duodenum, jejunum, ileum, proximal colon and distal colon amounted to 2.22, 4.79, 1.04, 0.27 and 0.25 mug/g ww, respectively. L-FABP tissue contents were markedly higher, amounting to 124 and 198 mug/g ww in duodenum and jejunum, and to 58, 26 and 44 mug/g ww in ileum, proximal colon and distal colon, respectively. Elevated plasma levels of both I-FABP and L-FABP were found in patients suffering from intestinal diseases, while only L-FABP was increased in cases of purely hepatocellular injury. CONCLUSIONS: I-FABP and L-FABP show a similar pattern of tissue distribution along the duodenal to colonal axis with highest tissue contents found in the jejunum but in each intestinal segment a >40-fold higher content of L-FABP than of I-FABP. Accordingly, besides I-FABP, also L-FABP is a useful plasma marker for the detection of intestinal injury, especially in patients undergoing intestinal surgery.

Adult↗

Cellular distribution and clinical value of urokinase-type plasminogen activator, its receptor, and plasminogen activator inhibitor-2 in esophageal squamous cell carcinoma.

To assess the participation of the plasminogen activation system in the invasiveness of esophageal squamous cell carcinoma, we performed immunohistochemistry and in situ hybridization to study the distribution of a urokinase-type plasminogen activator (u-PA), u-PA receptor (u-PAR), and plasminogen activator inhibitor-2 (PAI-2). u-PA and PAI-2 were expressed heterogeneously in cancer cells, and restricted expression was found in stromal cells, especially fibroblasts, that were located in the immediate proximity of the cancerous cells. u-PAR was found only in cancer cells located at the periphery of tumors. Compared with patients with u-PA-negative cancer cells, patients with u-PA-positive cancer cells more frequently showed a neoplastic invasion beyond the muscularis propria and lymph node metastases. They also showed a significantly shorter 5-year overall survival. Patients with PAI-2-positive fibroblasts showed significantly lower levels of local invasiveness, represented by a neoplastic invasion beyond the muscularis propria, than those who were PAI-2 negative. Our results suggest that the expression of u-PA in esophageal squamous cell carcinoma is predictive of poor survival, whereas the expression of PAI-2 in the fibroblasts surrounding them is protective. An analysis of u-PA and PAI-2 expression in cancer cells and their surrounding fibroblasts may be useful for predicting the prognosis of patients with esophageal squamous cell carcinoma.

Adult↗

A quantitative study of nuclear DNA of trophoblastic cells analysis of nuclear DNA distribution and clinical outcome of hydatidiform mole.

Microspectrophotometric measurements of the nuclear DNA contents of Feulgen-stained trophoblastic cells were made in the cases of 54 normal pregnancies, 10 missed abortions, 118 hydatidiform moles, 11 invasive moles, and 9 choriocarcinomas. The position of the main peak and the range of nuclear DNA distribution correlated well with the severity of the trophoblastic disease. A statistically significant correlation was found between the position of the main peak and the occurrence of secondary trophoblastic disease from hydatidiform mole. Histological grading of hydatidiform mole did not show a good correlation with regard to the occurrence of secondary trophoblastic disease from hydatidiform mole.

Cell Nucleus↗

Different O and K serotype distributions among clinical and environmental strains of Serratia marcescens.

Recent revision of the O serotyping scheme for Serratia marcescens has allowed the definitive serological identification of a collection of 511 epidemiologically distinct strains in terms of both lipopolysaccharide (O) antigens and capsular (K) antigens. High levels of typability were achieved, 88% and 91% respectively, with only 2% failing to type with either method. In most cases, non-typability was due to a lack of antigen, i.e., the strains produced only rough LPS or were acapsular, suggesting that typability would be little improved by the discovery of additional serotypes. The distribution of the 58 O:K serotypes was very uneven, with O14:K14 accounting for 30% of the 423 clinical strains in the collection, but only 5% of the 88 non-clinical, environmental strains. Thus, the prevalence of O14:K14 strains in hospitals is not reflected in the environment. Similar conclusions were valid for O27:K14, O21:K3 and O21:K14 strains, as well as those with rough lipopolysaccharide. Conversely, the proportions of O6:K3, O6:K14, O8:K14 or O28:K28 strains were significantly lower among the clinical collection than among their environmental counterparts (12% in total rather than 65%). This suggests that O14:K14 may have a selective advantage in colonising or infecting hospitalised patients and, therefore, that the O14 and K14 polysaccharides themselves may contribute towards the apparent pathogenicity of these serotypes.

Animals↗

Effect of knee component alignment on tibial load distribution with clinical correlation.

To determine ideal alignment and component placement of total knee prostheses, Kinematic (K) and total condylar (TC) devices were physiologically loaded and interface forces were measured. Laboratory observations were correlated with clinical (roentgenographic) findings. Asymmetric loading of the tibial component has been proposed as causing loosening and radiolucent lines. Misalignment of components is one factor that affects load sharing by bone under the medial and lateral regions of the tibial plateau. Tibial components of K and TC prostheses were inserted without cement into the cut surfaces of artificial tibiae. The mating femoral condylar components were mounted. The tibial and femoral components were individually positioned at 0 degrees (horizontal) and at certain angles of varus and valgus. Pressure-sensitive film was placed between the tibial component and the artificial tibia. A vertical load of 1500 N was used. The experiment was replicated twice. The percentages of the load on the medial and lateral regions of the tibial plateau were calculated from quantitative image analysis of the pressure patterns on the film. Roentgenograms from 532 K and 21 TC patients were examined to determine the orientations of the condylar and tibial components and the presence of radiolucent lines around the tibial component. An even distribution (ideal alignment) of load on the medial and lateral regions of the K tibial component occurred at 9 degrees of valgus tilt of the femoral component and 2 degrees of varus tilt of the tibial component and for the TC at 7 degrees valgus and 0 degrees varus. Misalignment by 5 degrees yielded a 7% change in the load distribution under the K plateau and a 40% change for the TC prosthesis; a 10 degrees misalignment produced changes of 34% and 62% for the K and TC, respectively. Small variations in clinical knee alignment produced the same percentage of radiolucent lines for each alignment group. The location of radiolucent lines was distributed among the medial, lateral, and both tibial plateaus regardless of knee alignment, although there were more medial reactions overall. The smallest incidence (8%) of radiolucent lines occurred with the K prosthesis at 7 degrees of knee valgus, the femoral component placed at 9 degrees valgus, and the tibial component at 2 degrees varus. This correlated with the ideal bench-test findings for the K device.

Humans↗

Diminutive polyps: histopathology, spatial distribution, and clinical significance.

This retrospective study of 329 diminutive colon polyps revealed that 49.2% of the polyps were neoplastic, whereas 49.9% were nonneoplastic. 36.8% of the polyps were metaplastic, and 0.9% had mixed metaplastic and adenomatous components. The metaplastic polyps had a predominance in the distal portion of the large bowel, with 76.9% being located distal from the splenic flexure and 52.9% being located in the rectosigmoid area. Neoplastic polyps were distributed throughout the colon, with 65.4% located from the splenic flexure distally and 34.5% located proximal to the splenic flexure. These findings suggest that a much larger proportion of diminutive polyps are neoplastic and therefore at risk to progress to carcinoma than previously considered.

Adult↗

Molecular evolution, species distribution, and clinical consequences of an endemic aminoglycoside resistance plasmid.

During the first 6 years after appearing in one hospital, a 92-kilobase conjugative plasmid, pBWH1, which encoded resistance to chloramphenicol and sulfonamides and determined TEM-1 beta-lactamase and 2''-aminoglycoside nucleotidyltransferase, underwent a variety of molecular changes. It was most prevalent initially in isolates of Klebsiella pneumoniae, then in isolates of Serratia marcescens, and finally, after nearly disappearing, in isolates of Enterobacter cloacae. Evolutionary changes in the plasmid did not account for its shifts in species distribution, since the original molecule was found in isolates of each species. The late resurgence of pBWH1 occurred after a copy of its original molecule entered a distinctive ornithine decarboxylase-negative strain of E. cloacae, new to the hospital. The resulting transconjugant strain, chromosomally resistant to topical silver salts and to cephalosporins, and with the addition of pBWH1-encoded aminoglycoside resistance, spread in the hospital by causing an outbreak of sepsis in the burn unit, where these were commonly used antibacterial agents. Thus, an endemic plasmid became prevalent in a new host species because one of its genes supplemented the fitness of an uncommon strain of the species for a particular clinical niche.

Aminoglycosides↗

Distribution of clinically relevant Borrelia genospecies in ticks assessed by a novel, single-run, real-time PCR.

A LightCycler-based PCR protocol was developed which targets the ospA gene for the identification and quantification of the different Borrelia burgdorferi sensu lato species in culture and in ticks, based on the use of a fluorescently labeled probe (HybProbe) and an internally labeled primer. The detection limit of the PCR was 1 to 10 spirochetes. A melting temperature determined from the melting curve of the amplified product immediately after thermal cycling allowed the differentiation of the three different B. burgdorferi sensu lato genospecies (B. burgdorferi sensu stricto, Borrelia garinii, and Borrelia afzelii) that are clinically relevant in Europe in a single PCR run. This method represents a simplified approach to study the association of different Borrelia species in ticks, the risk of Lyme borreliosis, and the putatively species-specific clinical sequelae. To determine the reliability of the real-time PCR protocol, we studied the prevalence of B. burgdorferi sensu lato infection in Ixodes ricinus ticks. A total of 1,055 ticks were collected by flagging vegetation in five different sites in the region of Konstanz (south Germany) and were examined for the distribution of B. burgdorferi species by real-time PCR. The mean infection rate was 35%. Of 548 adult ticks, 40% were positive, and of 507 nymphs, 30% were positive. The predominant genospecies (with 18% mixed infections) in the examined areas was B. afzelii (53%), followed by B. garinii (18%) and B. burgdorferi sensu stricto (11%); 0.8% of the infecting Borrelia could not be identified.

Animals↗

Major outer membrane proteins from Porphyromonas gingivalis: strain variation, distribution, and clinical significance in periradicular lesions.

Porphyromonas gingivalis has been implicated in both marginal periodontitis and periapical infection. This study examined the major outer membrane proteins, from P. gingivalis, which related to periradicular lesions. Outer membrane protein profiles of P. gingivalis ATCC 33277 and W83 were compared by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and N-terminal amino acid analysis. Most outer membrane proteins, such as RagA, gingipains, and OmpA-like proteins, were found in both strains in a similar distribution pattern; however, the migration positions of Lys-gingipain and RagB were inverted in SDS-PAGE. Western blot analysis showed that RagA, RagB, and OmpA-like proteins were found in all of the P. gingivalis strains tested. The antiserum of W83 against RagB reacted poorly to some strains, such as ATCC 33277. When strains phylogenetically related to P. gingivalis were examined, RagA and OmpA homologs were immunologically detected in several strains. However, none of the RagB homologs were detected in any strain analyzed, suggesting that RagB is unique to P. gingivalis. To examine immunoreactive antigens in P. gingivalis, sera from patients with periradicular lesions were used. More than half of the sera showed strong reactions to P. gingivalis cell components, especially RagB. Our results indicate that a major outer membrane protein, RagB, is a possible virulence factor in periradicular lesions.

Adhesins, Bacterial↗

Multidrug resistance among persons with tuberculosis in California, 1994-2003.

CONTEXT: Between 1994 and 2003, tuberculosis (TB) cases in California declined 33% (4834 to 3224). However, in 2003 California reported the largest number of cases in the nation, and over the past decade the proportion of cases with multidrug-resistant tuberculosis (MDR-TB) has not decreased. OBJECTIVE: To describe the magnitude, trends, geographic distribution, clinical characteristics, risk factors, and outcomes of MDR-TB cases reported to the California registry of Reports of Verified Cases of TB. DESIGN, SETTING, AND CASES: Analysis of 38,291 TB cases reported from all 61 local health jurisdictions in California during 1994-2003. Multidrug-resistant TB was defined as resistance to at least isoniazid and rifampin. MAIN OUTCOME MEASURES: Results of univariate and multivariable analyses of MDR-TB magnitude, trends, geographic distribution, clinical characteristics, associated factors, and outcomes. RESULTS: Of 38,291 reported TB cases, 28,712 (75%) were tested for resistance to at least isoniazid and rifampin; of these, 407 MDR-TB cases (1.4%) were reported from 38 of 61 California health jurisdictions (62%); the proportion of MDR-TB cases did not significantly change over the study period (P = .87). Cases of MDR-TB were twice as likely to have cavitary lesions compared with non-MDR-TB cases (P<.001) and were 7 times more likely to have reported previous treatment for TB (P<.001). Of MDR-TB cases with outcomes, 231 (67%) completed therapy, and those with MDR-TB were significantly less likely to complete therapy than those without MDR-TB (P<.001). Multivariate analysis identified previous TB diagnosis, positive acid-fast bacilli sputum smear results, Asian/Pacific Islander ethnicity, time in the United States less than 5 years at the time of diagnosis, and outcomes of "died" and "moved" as factors associated with MDR-TB. CONCLUSIONS: Multidrug-resistant TB, an airborne disease with limited, costly treatment options, persists in 1% to 2% of all cases despite California's control efforts. Local and global TB control efforts are needed to prevent the further development and spread of MDR-TB.

Adolescent↗

Thoracic paravertebral block: influence of the number of injections.

BACKGROUND AND OBJECTIVES: The purpose of this study was to assess the radiographic and clinical distribution of 1 to 4 paravertebral injections by use of the same total volume of local anesthetic mixture. METHODS: Sixty-nine patients scheduled for surgical interventions suitable for bilateral PVB were included in the study and were randomly assigned to 1 of 3 treatment groups. Group 1 received 4 paravertebral injections on one side versus 1 injection on the contralateral side (23 patients), group 2 received 4 injections versus 2 injections (23 patients), and group 3 received 4 injections versus 3 injections (23 patients). RESULTS: Sixty-one patients were included in the final analysis, which resulted in 368 thoracic paravertebral injections. Overall, 97% of the patients had adequate loss of sensation within the targeted area at the side of 4 injections, compared with only 11% for the single injections. The average vertical spread of contrast was found to be significantly greater in the set of 4 injections, with mean (SD) 6.5 (2.01) dermatomes, compared with the single injection, with 3.0 (1.19) dermatomes (P < .05). The average vertical spread of contrast and complete absence of sensation were significantly greater in the set of 4 injections compared with the set of 2 and 3 injections (P < .05). CONCLUSION: The main finding of the present study was that multiple paravertebral injections resulted in more reliable radiographic and clinical distribution compared with a single-injection technique.

Anesthetics, Local↗

Clinical training program for distributive pharmacists.

A training program to enable staff pharmacists in a state correctional system to shift their practice from distributive to clinical is described. Under a contract with the Texas Department of Criminal Justice (TDCJ), the University of Houston College of Pharmacy provides pharmaceutical services to 145,000 patients in 100 correctional facilities. An automated centralized distribution site was built in 1993 and four regional pharmacies were subsequently closed, resulting in the reallocation of eight distributive pharmacists positions to clinical services. Four of the eight pharmacists who would be displaced began a retraining program in preparation for decentralized clinical positions. The 18-month program, developed by university staff on contract to TDCJ and college faculty members, included 34 home-study modules, case studies, case presentations, seminars, and supervised practice experience. Three of the pharmacists completed the program, passed competency tests, and were certified for clinical practice privileges, including drug therapy assessment and written consultations. The three pharmacists now operate ambulatory care clinics at prison units. A clinical skills training program developed by a college of pharmacy correctional services division in cooperation with faculty members enabled staff pharmacists to convert their roles from distributive to clinical.

Education, Pharmacy, Continuing↗

[Studies on respiratory infections in primary care clinic (II). Distribution and antibiotic sensitivity to 45 agents of bacteria isolated from patients with respiratory infections visiting a doctor in private practice].

The bacteriology of the isolates from the sputum or the throat swab of patients with respiratory infections visiting a doctor in private practice in Sendai city during the period from March in 1988 to February in 1989 was documented, and their sensitivity to 45 antimicrobial agents was determined. Of the 568 patients, 514 cases had acute pharyngitis, 8 cases each had acute tonsillitis and acute bronchitis, 7 cases were acute pneumonia, 6 cases had herpangina, 18 cases had hand-foot-mouth disease with the signs of respiratory infections, 5 cases had varicella with the signs of respiratory infections and 2 cases were mumps with the signs of respiratory infections. Three hundred strains of potential (greater than or equal to 10(7) CFU/ml) pathogens were recovered from 293 of the 568 cases, which consisted of 124 strains of Haemophilus influenzae, 58 strains of Streptococcus pneumoniae, 45 strains of Staphylococcus aureus, 26 strains of Branhamella catarrhalis, 25 strains of Streptococcus pyogenes, 9 strains of Klebsiella pneumoniae and 13 strains of other species, not including non-fermentile gram-negative bacteria such as Pseudomonas aeruginosa and Acinetobacter calcoaceticus. Staphylococcus aureus and other strains were documented simultaneously in 6 out of 7 cases in which multi-organisms were recovered. Many strains of Staphylococcus aureus were isolated from young patients throughout the year. On the other hand many strains of Branhamella catarrhalis were isolated from elderly patients in winter. The sensitivity of 45 antimicrobial agents of 231 of 300 strains was determined by sensitivity disks (EIKEN, Japan). No strain of the Haemophilus influenzae in this study was resistant to ampicillin. None of the Streptococcus pneumoniae and Streptococcus pyogenes was resistant to ampicillin or cefazolin. None of the Staphylococcus aureus was resistant to cloxacillin, cefazolin, gentamicin or ofloxacin. We conclude from the above results that antibiotic-resistant strains are found presumably only in a very few cases in primary care clinic.

Anti-Bacterial Agents↗