Standard methods for creating digital skeletal models using structure-from-motion photogrammetry.

OBJECTIVES: This article assesses best practices for producing 3D digital cranial models through structure-from-motion (SfM) photogrammetry, and whether the metric accuracy and overall presentation of photogrammetric models are comparable to physical crania. It is intended to present a user-friendly standard method of creating accurate digital skeletal models using Agisoft PhotoScan. MATERIALS AND METHODS: Approximately 200 photographs were taken of three different crania, and were separated into series consisting of 50, 75, 100, 150, and approximately 200 photos. Forty-five cranial models were created using different photo series and a variety of PhotoScan settings. These models were assessed based on defined qualitative criteria, and model measurement estimates were compared with physical skeletal measurements using Bland-Altman plots. RESULTS: The majority of all models (37/45) produced measurement estimates with mean differences of 2 mm or less regardless of PhotoScan settings, and therefore demonstrated high levels of agreement with the physical measurements. Models created with 150 photographs and on "high" PhotoScan settings scored the highest in terms of qualitative appearance in the shortest amount of time. DISCUSSION: In PhotoScan, it is recommended to create cranial models using 150 photographs and "high" settings; this produces digital cranial models that are comparable to physical crania in both appearance and proportion. SfM photogrammetry is a convenient, noninvasive, and rapid 3D modeling tool that can be used in almost any setting to produce digital models, and following the guidelines established here will ensure that these models are metrically accurate.

ALK Rearrangements Are Infrequent in Cellular Blue Nevus and Deep Penetrating Nevus.

Recent studies have identified kinase fusions in Spitzoid melanocytic neoplasms, and approximately 10% of Spitzoid neoplasms harbor anaplastic lymphoma kinase (ALK) rearrangements and corresponding ALK immunoreactivity. Deep penetrating nevi (DPN), a subset of melanocytic neoplasms, have histologic and immunohistochemical overlap that have historically supported classification of DPN with blue/cellular blue nevi (CBN). However, HRAS mutations have rarely been detected in DPN, thereby also linking them to Spitz nevi. The purpose of this study was to see if DPN or CBN possess ALK rearrangements, thereby providing more evidence that these melanocytic lesions may be pathogenetically related to Spitzoid neoplasms. Using ALK immunohistochemistry as a surrogate for ALK rearrangement, the authors examined 26 DPN, 30 CBN, and 4 conventional blue nevi. ALK immunoreactive cases underwent fluorescent in situ hybridization to investigate for the presence of ALK gene rearrangement. Patchy and focal ALK immunostaining was found in only 1 case of DPN (1/26, 3.8%). Seven cases of CBN (7/30; 23%) showed ALK immunostaining (6 focal/patchy, 1 strong and diffuse). Fluorescent in situ hybridization using ALK break-apart probes showed various degrees of gain of 2p23 and rare ALK break-apart signals. Four CBN showed ALK rearrangement in 2%-4% of cells. Two cases of CBN showed gain of 2p23 in 10%-20% of cells. In our study, ALK rearrangements are uncommon in both CBN and DPN, making ALK an unlikely driver in tumorigenesis and classification of these melanocytic variants. However, our study did identify ALK molecular changes and immunohistochemical staining patterns that have not been previously described in CBN or DPN.

Remission of refractory granulomatous primary cutaneous anaplastic large cell lymphoma to brentuximab vedotin.

Primary cutaneous anaplastic large cell lymphoma (PC-ALCL) is a rare non-Hodgkin's lymphoma that arises as a single, or multiple dome-shaped tumours on the skin. The histology is characterised by the presence of atypical lymphocytes with large irregularly shaped nuclei that express the surface marker CD30. There can be significant heterogeneity in clinical manifestation and histological pattern and in rare cases accurate diagnosis can be a challenge. Here, we present an unusual case presentation of cutaneous CD30+ anaplastic large cell lymphoma with significant granulomatous histology pattern that mimicked sarcoid. After a lack of durable response to treatments that included glucocorticoid and methotrexate, targeted treatment with anti-CD30 monoclonal antibody drug conjugate (brentuximab vedotin) yielded long-term clinical remission.

Gastrin Staining in Inflamed Stomach Biopsies Labeled as "Antral" Rarely Detects Atrophic Gastritis.

OBJECTIVES: Autoimmune metaplastic atrophic gastritis (AMAG) is an underrecognized entity, especially in its early stage. This study assessed whether the use of gastrin immunohistochemistry would increase sensitivity for diagnosing early AMAG. METHODS: Three-hundred gastric biopsies were prospectively stained for gastrin by immunohistochemistry. Inclusion criteria included well-oriented gastric mucosa with mucus glands and minimal plasma cell infiltrate not suspected to represent pyloric metaplasia. Patient age, sex, designated location of biopsy, presence or absence of intestinal metaplasia, and clinical information were not criteria. Any case with absence of gastrin-positive endocrine cells reflexed to chromogranin immunohistochemistry. Maloriented biopsies or cases with current Helicobacter infection were excluded. RESULTS: The 298-patient study cohort comprised 222 females (mean age, 47 years; range, 16-80 years) and 76 males (mean age, 49 years; range, 7-80 years). Biopsies were designated as "antral/antral nodules" (61%), and the rest were labeled "gastric/random stomach" (39%). Nine cases (3%) exhibited absence of gastrin-positive endocrine cells; one of those showed endocrine cell hyperplasia by chromogranin staining. CONCLUSIONS: Pathologists should be aware of the histologic features of early AMAG and meticulously analyze tissue regardless of specimen labeling. Gastrin immunostain is a supplemental diagnostic tool when encountering inflamed antral-appearing specimens.

Comparative pharmacokinetics of propofol in Chinese adults and children.

The pharmacokinetics of propofol were studied in 14 healthy young male Chinese adults, aged 18-38 years, undergoing minor orthopedic surgery. All patients who received a single bolus dose of propofol 2.5 mg/kg were paralyzed with atracurium and mechanically ventilated. Anesthesia was maintained with 67% nitrous oxide plus 1-2% isoflurane in oxygen with alfentanil 5 micrograms/kg intravenously as a bolus injection. Blood concentrations of propofol over the subsequent 24 hours were measured using high pressure liquid chromatography with fluorimetric detection. Data were consistently described by a three compartment model but analysis revealed two significantly different blood propofol concentration-time profiles (p less than 0.05). Five patients, designated "fast" metabolizers, demonstrated a mean elimination half-life which was shorter than that described in Chinese children, while their total body clearance was similar. Nine other patients, designated "slow" metabolizers, had a longer mean elimination half-life and slower total body clearance than those in elderly Caucasian patients. This may be suggestive of propofol metabolism at some extra-hepatic site in some patients, while other patients demonstrate marked lipophilicitic constraint of the drug by the deep compartment.

Pharmacokinetics of propofol in children.

The pharmacokinetics of propofol were studied in 12 healthy Chinese children, aged 4-12 yr, undergoing circumcision under inhalation anaesthesia. All patients received a single i.v. bolus dose of propofol 2.5 mg kg-1 and blood concentrations of propofol over the subsequent 24 h were measured using high pressure liquid chromatography with fluorimetric detection. Data were consistent with a three-compartment model with a mean (SEM) elimination half-life of 209 (29) min and total body clearance of 40.4 (3.6) ml min-1 kg-1. The mean (SEM) apparent volume of distribution at steady state was 5.0 (2.7) litre kg-1 and volume of the central compartment was 0.6 (0.1) litre kg-1. The mean (SEM) ratio of k12:k21 was 1.4 (0.2), suggesting that, after injection of a single bolus dose in children, propofol is distributed rapidly to the shallow compartment. The mean ratio of k31:k10 suggests that lipophilicity constrains return of the drug to the central compartment.

Trivial pursuit.

I commend Nurse Snowden (Letters, Nursing Standard week ending December 19) for putting forward the patients' view. However one must be cautious in interpreting people's views; I have heard suggestions on uniform from some male patients that I doubt Nursing Standard would print (unless on page 3? ). It is essential to see such views in context- for example, if she were to ask 'what do you think is most professional for a nurse, a smart cap or a high standard of nursing?' she might not get 100 per cent in favour of caps.

Antagonism of the hypnotic effect of midazolam in children: a randomized, double-blind study of placebo and flumazenil administered after midazolam-induced anaesthesia.

In a randomized, double-blind study, we administered placebo and flumazenil to 40 healthy Chinese boys, aged 3-12 yr, undergoing circumcision. The children received midazolam 0.5 mg kg-1 orally for premedication and 0.5 mg kg-1 i.v. during induction. After operation the patients were given 0.1 ml kg-1 of a blinded solution followed by 0.05 ml kg-1 min-1 until either they awoke or the 10-ml ampoule of solution was empty. Efficacy of antagonism of midazolam was assessed by times to eye opening and self identification, modified Steward coma scale, a post-box toy completion-time ratio and qualitatively by an independent observer. The difference between flumazenil and placebo was both clinically and statistically different in the first 2 h. Children receiving flumazenil awoke approximately four times faster and identified themselves nearly three times sooner; 65% of this group could complete the post-box toy at 10 min, compared with none of the placebo group. There were no cases of resedation, but one child did not awaken for 30 min after i.v. administration of flumazenil 1.0 mg. The mean total dose of flumazenil administered was 0.024 (SD 0.019) mg kg-1. Flumazenil rapidly antagonized midazolam-induced hypnosis in children and was associated with minimal change in cardiorespiratory variables.

Physical map and characterization of transcripts in the candidate interval for familial chondrocalcinosis at chromosome 5p15.1.

The gene for familial chondrocalcinosis (MIM 118600; gene symbol CCAL2) has been localized to a 0.8-cM interval on the short arm of chromosome 5, between the polymorphic microsatellite markers D5S416 and D5S2114. We have undertaken the physical and transcript mapping of this interval, as well as regions telomeric to the interval, in an attempt to define ultimately the gene for this disorder. The physical map is composed of YAC, BAC, PAC, and cosmid resources and spans a physical distance of approximately 0.3 Mb. Using cDNA selection, we have identified eight novel transcripts in and around the interval; two of the selected transcripts reside in the candidate interval. We have also more precisely placed several expressed sequence tags (ESTs) that were previously mapped by radiation hybrid analysis and were reported to reside in or near the candidate interval. Two of the ESTs analyzed overlap with the selected cDNAs that reside in the candidate interval. All of the selected cDNAs are expressed partial transcripts, as determined by Northern blot analysis, and using RT-PCR analysis, we have determined that the cDNAs that reside in the candidate interval are expressed in cartilage and synovium, tissues that are presumably relevant to the chondrocalcinosis phenotype.

Evaluation of S. aureus ID, a new chromogenic agar medium for detection of Staphylococcus aureus.

S. aureus ID (bioMérieux, La Balme Les Grottes, France) is a new chromogenic agar medium designed to enable the isolation of staphylococci and the specific identification of Staphylococcus aureus. S. aureus produces green colonies on this medium due to production of alpha-glucosidase. To evaluate this medium, a total of 350 wound swabs were cultured onto S. aureus ID, CHROMagar Staph. aureus, and conventional media routinely used in our laboratory. After 18 to 20 h of incubation, 96.8% of strains formed green colonies on S. aureus ID compared with 91.1% of strains forming mauve colonies on CHROMagar Staph. aureus. A total of 94.3% of strains were recovered within 18 to 20 h with conventional media. The sensitivity was increased after 48 h of incubation to 98.7, 96.2, and 95.6% with S. aureus ID, CHROMagar Staph. aureus, and conventional media, respectively. A total of 97.4% of green colonies on S. aureus ID were confirmed as S. aureus compared with 94.4% of mauve colonies on CHROMagar Staph. aureus. We conclude that S. aureus ID is a highly sensitive and specific medium for the isolation and identification of S. aureus from wound swabs.

Development and evaluation of a chromogenic agar medium for methicillin-resistant Staphylococcus aureus.

We describe here the development and evaluation of MRSA ID, a new chromogenic agar medium for the specific isolation and identification of methicillin-resistant Staphylococcus aureus (MRSA). We used S. aureus ID (bioMerieux, La Balme Les Grottes, France) and supplemented it with various antimicrobials, including cefoxitin, ciprofloxacin, oxacillin, and methicillin. Cefoxitin proved to be superior to the other antimicrobials for the selection of MRSA from other strains of S. aureus. MRSA ID (consisting of S. aureus ID supplemented with 4 mg of cefoxitin/liter) was evaluated by the use of 747 swabs from various clinical sites. All specimens were also cultured on CHROMagar MRSA and oxacillin resistance screening agar base (ORSAB) and in selective mannitol broth (SMB). A total of 85 MRSA strains were isolated by a combination of all methods. After 22 to 24 h of incubation, 80% of the MRSA strains were isolated as green colonies on MRSA ID, compared with 59 and 62% of the strains that were isolated as colored colonies on CHROMagar MRSA and ORSAB, respectively. After 48 h of incubation, 89, 72, and 78% of the MRSA strains were isolated on MRSA ID, CHROMagar MRSA, and ORSAB, respectively. Sixty-five percent of the strains were isolated by growth in SMB. The specificities of MRSA ID, CHROMagar MRSA, ORSAB, and SMB were 99.5, 99.3, 97.9, and 92.8%, respectively, after 22 to 24 h of incubation. We conclude that MRSA ID is a sensitive and specific medium for the isolation and identification of MRSA.

Refinement of the chromosome 5p locus for familial calcium pyrophosphate dihydrate deposition disease.

Familial calcium pyrophosphate dihydrate deposition disease (CPPDD) is a disease of articular cartilage that is radiographically characterized by chondrocalcinosis due to the deposition of calcium-containing crystals in affected joints. We have documented the disease in an Argentinean kindred of northern Italian ancestry and in a French kindred from the Alsace region. Both families presented with a common phenotype including early age at onset and deposition of crystals of calcium pyrophosphate dihydrate in a similar pattern of affected joints. Affected family members were karyotypically normal. Linkage to the short arm of chromosome 5 was observed, consistent with a previous report of linkage of the CPPDD phenotype in a large British kindred to the 5p15 region. However, recombinants in the Argentinean kindred have enabled us to designate a region<1 cM in length between the markers D5S416 and D5S2114 as the CPPDD locus.