Design of a virtual data shelf to effectively explore a large database of 3D medical surface models in VR.

PURPOSE: Medical researchers deal with a large amount of patient data to improve future treatment decisions and come up with new hypotheses. To facilitate working with a large database containing many patients and parameters, we propose a virtual data shelf, displaying the 3D anatomical surface models in an immersive VR environment. METHODS: Thereby, different functionalities such as sorting, filtering and finding similar cases are included. To provide an appropriate layout and arrangement of 3D models that optimally supports working with the database, three layouts (flat, curved and spherical) and two distances are evaluated. A broad audience study with 61 participants was conducted to compare the different layouts based on their ease of interaction, to get an overview and to explore single cases. Medical experts additionally evaluated medical use cases. RESULTS: The study revealed that the flat layout with small distance is significantly faster in providing an overview. Applying the virtual data shelf to the medical use case intracranial aneurysms, qualitative expert feedback with two neuroradiologists and two neurosurgeons was gathered. Most of the surgeons preferred the curved and spherical layouts. CONCLUSION: Our tool combines benefits of two data management metaphors, resulting in an efficient way to work with a large database of 3D models in VR. The evaluation gives insight into benefits of layouts as well as possible use cases in medical research.

Optimized signal deduction procedure for the MIEZE spectroscopy technique.

A method is reported to determine the phase and amplitude of sinusoidally modulated event rates, binned into four bins per oscillation, based on data generated at the resonant neutron spin-echo spectrometer RESEDA at FRM-II. The presented algorithm relies on a reconstruction of the unknown parameters. It omits a calculation-intensive fitting procedure and avoids contrast reduction due to averaging effects. It allows the current data acquisition bottleneck at RESEDA to be relaxed by a factor of four and thus increases the potential time resolution of the detector by the same factor. The approach is explained in detail and compared with the established fitting procedures of time series having four and 16 time bins per oscillation. In addition the empirical estimates of the errors of the three methods are presented and compared with each other. The reconstruction is shown to be unbiased, asymptotic and efficient for estimating the phase. Reconstructing the contrast increases the error bars by roughly 10% as compared with fitting 16 time-binned oscillations. Finally, the paper gives heuristic, analytical equations to estimate the error for phase and contrast as a function of their initial values and counting statistics.

Facilitated nuclear transport of calmodulin in tissue culture cells.

Calmodulin (CaM) potentiates Ca(2+)-dependent signaling pathways in both the cytoplasm and nucleus. We have investigated the mechanism of CaM nuclear transport using tissue culture cell microinjection and a permeabilized cell import assay. The inhibition of CaM import by the translocation inhibitor wheat germ agglutinin (WGA) and by chilling, indicates that CaM import is facilitated, but because ATP depletion does not affect CaM import, the mechanism does not appear to be active. Chilling and WGA arrest persist in ATP-depleted cells, indicating that CaM is not retained in the cytoplasm by an ATP-dependent mechanism. In permeabilized cells, both Ca(2+)-CaM and Ca(2+)-free CaM are sensitive to extract-dependent WGA and chilling import inhibition. Titration experiments in microinjected and permeabilized cells indicate that a saturable cytosolic factor(s) mediates chilling and WGA arrest.

In vivo nuclear transport kinetics in Saccharomyces cerevisiae: a role for heat shock protein 70 during targeting and translocation.

The transport of proteins into the nucleus is a receptor-mediated process that is likely to involve between 50-100 gene products, including many that comprise the nuclear pore complex. We have developed an assay in Saccharomyces cerevisiae for the nuclear transport of green fluorescent protein fused to the SV-40 large T antigen nuclear localization signal (NLS-GFP). This assay allows the measurement of relative NLS-GFP nuclear import rates in wild-type and mutant cells under various physiological conditions. Probably the best understood component of the nuclear transport apparatus is Srp1p, the NLS receptor, which binds NLS-cargo in the cytoplasm and accompanies it into the nucleus. When compared to SRP1+ cells, NLS-GFP import rates in temperature-sensitive srp1-31 cells were slower and showed a lower temperature optimum. The in vivo transport defect of the srp1-31 cells was correlated with the purified protein's thermal sensitivity, as assayed by in vitro NLS peptide binding. We show that the kinetics of NLS-directed nuclear transport in wild-type cells is stimulated by the elevated expression of SSA1, which encodes a cytoplasmic heat shock protein 70 (Hsp70). Elevated Hsp70 levels are sufficient to suppress the NLS-GFP import defects in srp1-31 and nup82-3 cells. NUP82 encodes a protein that functions within the nuclear pore complex subsequent to docking. These results provide genetic evidence that Hsp70 acts during both targeting and translocation phases of nuclear transport, possibly as a molecular chaperone to promote the formation and stability of the Srp1p-NLS-cargo complex.

Laparoscopic surgery in children is associated with an intraoperative hypermetabolic response.

BACKGROUND: Laparoscopic surgery is thought to be associated with a reduced metabolic response compared to open surgery. Oxygen consumption (VO2) and energy metabolism during laparoscopic surgery have not been characterized in children. METHODS: We measured respiratory gas exchange intraoperatively in children undergoing 19 open and 20 laparoscopic procedures. Premature infants and patients with metabolic, renal, and cardiac abnormalities were excluded. Anesthesia was standardized. Unheated carbon dioxide was used for insufflation. VO2 was measured by indirect calorimetry. Core temperature was measured using an esophageal temperature probe. RESULTS: We found a steady increase in VO2 during laparoscopy. The increase in VO2 was more marked in younger children and was associated with a significant rise in core temperature. Open surgery was not associated with significant changes in core temperature or VO2. CONCLUSIONS: Laparoscopy in children is associated with an intraoperative hypermetabolic response characterized by increased oxygen consumption and core temperature. These changes are more marked in younger children.

Successful resection of a congenital superior mesenteric arteriovenous malformation.

A 15-month-old male presented with severe gastrointestinal bleeding and heart failure. Imaging revealed a superior mesenteric artery arteriovenous malformation, associated with a congenital portosystemic shunt. The heart failure was cured by resection of the arteriovenous malformation.

High complete response rate in children with advanced germ cell tumors using cisplatin-containing combination chemotherapy.

A consecutive series of 13 children (five girls) with advanced malignant germ cell tumors (MGCTs) were treated with between four and seven (median, six) courses of cisplatin, bleomycin, and either vinblastine (BVP) or VP-16 (BEP). There were seven gonadal primaries (four testis, three ovary) and six at extragonadal sites (three sacrococcyx, two thoracic, one extradural). Total or subtotal removal of primary tumor was carried out in nine patients at diagnosis and two others after some chemotherapy. Clinical complete remission (CR) was achieved in nine of ten patients with measurable disease and serum markers returned to normal in all 13 patients. Eleven remain disease-free 17 to 48 months (median, 28 months) after diagnosis. One patient (stage IV sacrococcygeal tumor) relapsed at the primary site 3 months after completing treatment, but is disease-free after further surgery, radiotherapy, and chemotherapy. Serial glomerular filtration rates were performed during treatment. Audiometry and pulmonary function tests were carried out where possible. Toxicity led to alteration of drug scheduling in two cases, but there were no permanent clinical renal, auditory, or pulmonary sequelae. These encouraging results confirm that MGCTs in children are as responsive as those in adults to cisplatin-containing chemotherapy and indicate that they may be as curable. The regimens are relatively well-tolerated and, with close monitoring, clinically significant toxicity should be avoidable.

Seamless management of biliary atresia in England and Wales (1999-2002).

BACKGROUND: Before 1999, infants born in the UK with suspected biliary atresia were investigated in regional centres, and, if confirmed, a Kasai operation was done there. Since 1999, all infants with suspected biliary atresia in England and Wales, UK, have been referred to one of three designated centres where both the Kasai operation and liver transplantation (if necessary) could be done. METHODS: We assessed clearance of jaundice (bilirubin <20 micromol/L) as an early outcome in all cases of biliary atresia referred from one of the three centres. We then estimated survival using the Kaplan-Meier method with endpoints of liver transplantation or death. FINDINGS: 148 infants with biliary atresia were treated between January, 1999, and June, 2002. A primary portoenterostomy was done in 142 (96%) infants and a primary liver transplant in five (3%). One child died before any intervention. Early clearance of jaundice after portoenterostomy was achieved in 81 of 142 (57%) infants. Liver transplantation was done in 52 (37%) of those undergoing portoenterostomy. 13 (9%) infants died. Of the 135 children who survived, 84 (62%) still have their native liver and 51 (38%) had transplantation. The median follow-up of survivors was 2.13 (range 0.5-4.1) years. The overall 4-year estimated actuarial survival was 89% (95% CI 82-94). The 4-year estimated actuarial survival with native liver was 51% (42-59%). INTERPRETATION: Our early results suggest that surgical outcome can be improved by centralisation of care to supra-regional centres.

Resection and primary anastomosis is a valid surgical option for infants with necrotizing enterocolitis who weigh less than 1000 g.

HYPOTHESIS: Primary anastomosis following intestinal resection is a valid surgical option in the treatment of infants with necrotizing enterocolitis (NEC) who weigh less than 1000 g. DESIGN: Retrospective case series. SETTING: Tertiary neonatal surgery referral center. PATIENTS: All infants with confirmed NEC weighing less than 1000 g admitted to our intensive care unit over 4 years. INTERVENTION: For infants requiring laparotomy and intestinal resection, primary anastomosis was performed whenever the clinical condition permitted. MAIN OUTCOME MEASURES: Short- and long-term survival, length of intensive care unit stay, and complications. RESULTS: Fifty-one infants with NEC who weighed less than 1000 g were admitted during the study period. Twelve infants underwent intestinal resection and primary anastomosis (median weight at surgery, 0.83 kg; range, 0.6-0.96 kg). One infant developed recurrent NEC, requiring further surgery, but there were no anastomotic leakages and no strictures. The median postoperative stay on our intensive care unit was 14 days (range, 2-49 days). All 12 infants survived their episode of acute NEC, and 8 are alive, with a median follow-up of 34.2 months (range, 4.7-48.4 months). Only 1 death was related to NEC. During the same period, 14 infants underwent intestinal resection and stoma formation. Ten survived the acute episode, and 6 are alive at a median follow-up of 24.0 months (range, 13.1-33.9 months). The median postoperative intensive care unit stay was 18 days (range, 2-74 days). Necrotizing enterocolitis-related complications occurred in 8 of these infants. CONCLUSIONS: The outcome of infants with NEC who weigh less than 1000 g and undergo primary anastomosis is comparable to that of infants treated using alternative techniques. It is, therefore, a valid surgical option in selected infants. The mortality in this group of infants is high.

Detection and affinity purification of beta-endorphin precursors using a monoclonal antibody.

A monoclonal antibody to porcine beta-lipotropin has been produced which binds to the N-terminal (gamma-lipotropin) portion of the molecule. The antibody can be used to detect beta-lipotropin as well as other beta-endorphin precursors (predominantly a Mr 38 000 polypeptide) using radiobinding assay or the immunoblotting technique. Purification of the peptides can be readily achieved by affinity chromatography using the monoclonal antibody covalently bound to Sepharose 4B. As the antibody recognises the N-terminal part of beta-lipotropin, it can be used to detect and purify beta-lipotropin and other beta-endorphin precursors in the presence of beta-endorphin.

Intrasplenic primary immunization for the production of monoclonal antibodies.

A novel immunization procedure for eliciting monoclonal antibodies ( McAbs ) is described. With intrasplenic inoculation only small amounts of immunogen are required. As little as 20 micrograms of protein antigen or 2.5 X 10(5) cells have been found sufficient to immunize mice or rat spleen cells for the production of specific McAbs . A high proportion of hybridomas secreting McAbs against cell surface antigens and soluble proteins has been obtained with this immunization procedure. The system could facilitate McAb production in many instances in which only small quantities of immunogen are available.

Use of 'single shot' intrasplenic immunization for production of monoclonal antibodies specific for human IgM.

We report here the use of 'single shot' intrasplenic injection of human IgM for immunization of mice to obtain splenocytes for use in the production of hybridomas secreting antibodies against human IgM. Fusion was performed 3 days after intrasplenic injection of 20 micrograms of myeloma IgM. IgM-specific antibodies were found in 12% of the fusion wells; only 1 well contained antibodies which cross-reacted with other immunoglobulin classes. Two monoclonal antibodies (McAbs) have been fully characterized as specific for different epitopes on Fc mu. These antibodies can be used to detect IgM on the surface of human B cells by immunofluorescence and in solution by solid-phase radiobinding assay or single radial immunodiffusion. Both McAbs can also detect IgM fragments by immunoblotting from non-reducing SDS-polyacrylamide gels.

Chemotherapy effects on hepatoblastoma. A histological study.

The histopathological features of hepatoblastoma in 17 patients treated with preoperative chemotherapy were compared with those in 11 patients not subjected to chemotherapy during the same 11-year period. Tumor necrosis was more extensive in patients receiving preoperative chemotherapy. Two tumors, however, were apparently unaffected by chemotherapy. There was no obvious correlation between the extent of necrosis and the number of courses of chemotherapy. There also seems to be no evidence of preferential ablation of a particular morphological type of tumor. The most notable feature in cases treated with chemotherapy was the extensive presence of osteoid. Osteoid was present in 36% of untreated cases, occupying < 5% of the surface area, compared with 82% in the treated group. In seven cases, osteoid occupied > 40% of the surface area. This finding raises speculation about the role of chemotherapy in the maturation of tumors that have an inherent ability to differentiate. A long-term study is needed to clarify the prognostic significance of mature heterologous elements in hepatoblastoma.

Expression of a high molecular weight form of insulin-like growth factor II in a Beckwith-Wiedemann syndrome associated adrenocortical adenoma.

Beckwith-Wiedemann syndrome is a rare condition (1/13,700 live births) occurring in both inherited and sporadic forms in the population. It is manifest as a fetal overgrowth syndrome, in which hypertrophy dominates the clinical picture. An additional complication is that these children are predisposed to a specific subset of childhood neoplasms, amongst which are Wilms' tumour and adrenocortical carcinoma. We report here the synthesis by an associated adrenal tumour of large quantities of a high molecular weight form of insulin-like growth factor II (IGF-II), associated with profound suppression of circulating IGFs in the patient's serum. As with other tumours of this type, the tumours showed loss of material on chromosome 11p.

Oesophageal atresia, related malformations, and medical problems: a family study.

Oesophageal atresia (OA) and tracheo-oesophageal fistula (TOF) are life-threatening malformations of generally undefined cause. Previous reports of familial cases suggest a genetic contribution. The pattern of inheritance appears non-Mendelian, i.e., multifactorial. Individuals with OA/TOF often have other malformations and medical problems. The aim of this study was to determine the association in OA/TOF cases and healthy control subjects of associated malformations, midline defects, and medical conditions. We also investigate the relationships of these conditions in the relatives of the cases and controls. The results show that infants with OA/TOF frequently have VACTERL anomalies (vertebral, 17%; anal, 12%; cardiac, 20%; renal, 16%; limb, 10%) and other midline defects (cleft lip and palate, 2%; sacral dysgenesis, 2%; urogenital anomalies, 5%). The following medical problems were also reported: oesophageal dysmotility, 21%; gastro-oesophageal reflux, 22%; chest infections, 6%; and autonomic dysfunction, 0.5%. The first-degree relatives of children with OA are much more likely to have one of the aforementioned malformations or medical conditions when compared with the control group: one or more VACTERL anomalies (P < 0.01), gastro-oesophageal reflux (P < 0.05), recurrent respiratory infections (P < 0.05), and autonomic dysfunction (P < 0.001). The more distant relatives also show an increased incidence of such problems although in this case the data must be viewed with caution. The results confirm that the associated malformations and related medical problems occur significantly more frequently in the relatives of individuals with OA/TOF. These families may prove valuable for linkage analysis in an attempt to determine the genetics of OA/TOF.

A histopathological study of gastric mucosal biopsies in infantile hypertrophic pyloric stenosis.

Gastric biopsies from 35 infants with hypertrophic pyloric stenosis have been assessed for histological features of gastritis. No erosions were found, and there was no excess cellular infiltration of the lamina propria compared with a control group. Fresh haemorrhage into the lamina propria was frequent in both pyloric stenosis and control sections.

Experience with a cholinesterase histochemical technique for rectal suction biopsies in the diagnosis of Hirschsprung's disease.

Cryostat sections from 160 rectal suction biopsies were stained for cholinesterases by the method of Karnovsky and Roots (1964) in an attempt to facilitate the diagnosis of Hirschsprung's disease. The method proved at least as reliable as experienced assessment of paraffin haematoxylin-eosin sections, and appeared to offer the advantages of reduced scanning fatigue and superior demonstration of the increased cholinesterase-positive nerves in Hirschprung's disease. Contrary to the findings of Meier-Ruge (1971) it was not possible to base a diagnosis on mucosal cholinesterase activity.

The surgical management of neonatal necrotizing enterocolitis.

Twelve infants with necrotizing enterocolitis were treated surgically in the 2 year period from 1973 to 1974. Resection of gangrenous intestine and proximal enterostomy was preferred in 11 patients. There were four deaths: two were grossly premature infants, one died from electrolyte disturbances related to the proximal enterostomy, and one was an apparent cot death. Intravenous nutrition was used routinely in all cases in the postoperative period. The problems of recommencement of enteral feeding and ileostomy dysfunction are discussed briefly.

Antibodies to poliovirus detected by immunoradiometric assay with a monoclonal antibody.

An immunoradiometric assay (IRMA) for the assay of antibodies to poliovirus antigens is described. Dilutions of the test sera or whole (finger prick) blood samples were incubated with the Poliovirus antigen bound to a solid phase and the specific antibody was detected by the addition of a mouse anti-human IgG monoclonal antibody (McAb), which was itself revealed by iodinated sheep IgG anti-mouse F(ab). We have shown that this technique is suitable for the estimation of IgG anti-poliovirus antibodies induced in children following polio vaccine. The present study shows that SPRIA provides a simple and inexpensive method for serological studies with poliovirus particularly for use in large-scale surveys.

Associated urologic anomalies in low imperforate anus are capable of causing significant morbidity: a 15-year experience.

OBJECTIVES: To determine the incidence and morbidity caused by urologic anomalies in patients with low imperforate anus. METHODS: The case records and imaging studies of 95 patients who underwent surgery for low imperforate anus over a 15-year period were retrospectively reviewed. Follow-up ranged from 2 to 18 years (mean 5.4). RESULTS: Genitourinary abnormalities were seen in 29 patients (31%), whereas 10 (11%) had lumbosacral abnormalities. A micturating cystourethrogram was performed in 48 patients, 18 of whom were shown to have vesicoureteric reflux and 2 of whom required surgical correction. Three additional patients required bilateral ureteric reimplantation: 2 had megaureters whereas 1 had bilateral ectopic ureters. Four patients had evidence of chronic renal failure; these included 1 patient with reflux nephropathy, 2 with bilateral dysplastic kidneys, and 1 with neurogenic bladder. The patient with reflux nephropathy underwent renal transplantation at the age of 18 years. Two patients had proximal hypospadias and 4 had undescended testes. A neurogenic bladder was documented in 5 children, 4 of whom had lumbosacral abnormalities. One of these had a spinal lipoma and required excision of the lipoma and untethering of the spinal cord. CONCLUSIONS: We conclude that 30% of patients with low imperforate anus would have associated urologic anomalies, several of which are capable of causing significant morbidity. Thus, all patients with imperforate anus, whether high or low, need to be screened for associated urologic anomalies.