On the dose sensitivity of a new CDMAM phantom.

For the technical quality assurance of breast cancer screening protocols several phantoms have been developed. Their dose sensitivity is a common topic often discussed in literature. The European protocol for the quality control of the physical and technical aspects of mammography screening suggests a contrast-detail phantom like the CDMAM phantom (Artinis Medical Systems, Elst, NL). The CDMAM 3.4 was tested with respect to its dose sensitivity and compared to other phantoms in a recent paper. The CDMAM 4.0 phantom provides other disc diameters and thicknesses adapted more closely to the image quality found in modern mammography systems. This motivates a comparison of the two generations using the same exposure parameters. We varied the time-current (mAs) within a range of clinically used values (40-140 mAs). All evaluations were done using automatic evaluation software provided by Artinis (for CDMAM 4.0) and the National Coordinating Centre for the Physics of Mammography, Guildford UK (CDMAM 3.4). We compared the relative dose sensitivity with respect to the different diameters and also computed the IQFinv parameter, which averages over the diameters as suggested in the manual for the phantom. The IQFinv parameter linearly depends on dose for both phantoms. The CDMAM 4.0 shows a more monotonous dependence on dose, the total variation of the threshold thicknesses as functions of the dose are significantly smaller than with the CDMAM 3.4. As the automatic evaluation shows rather different threshold thicknesses for the two phantoms, conversion factors for human to automatic readout have to be adapted.

A navigation system for flexible endoscopes using abdominal 3D ultrasound.

A navigation system for flexible endoscopes equipped with ultrasound (US) scan heads is presented. In contrast to similar systems, abdominal 3D-US is used for image fusion of the pre-interventional computed tomography (CT) to the endoscopic US. A 3D-US scan, tracked with an optical tracking system (OTS), is taken pre-operatively together with the CT scan. The CT is calibrated using the OTS, providing the transformation from CT to 3D-US. Immediately before intervention a 3D-US tracked with an electromagnetic tracking system (EMTS) is acquired and registered intra-modal to the preoperative 3D-US. The endoscopic US is calibrated using the EMTS and registered to the pre-operative CT by an intra-modal 3D-US/3D-US registration. Phantom studies showed a registration error for the US to CT registration of 5.1 mm±2.8 mm. 3D-US/3D-US registration of patient data gave an error of 4.1 mm compared to 2.8 mm with the phantom. From this we estimate an error on patient experiments of 5.6 mm.

Dose sensitivity of three phantoms used for quality assurance in digital mammography.

Technical quality assurance (QA) is one of the key issues in breast cancer screening protocols. For this QA task, three different methods are commonly used to assess image quality. The European protocol suggests a contrast-detail phantom (e.g. the CDMAM phantom), while in North America the American College of Radiology (ACR) accreditation phantom is proposed. Alternatively, phantoms based on image quality parameters from applied system theory such as the noise-equivalent number of quanta (NEQ) are applied (e.g. the PAS 1054 phantom). The aim of this paper was to correlate the changes in the output of the three evaluation methods (CDMAM, ACR and NEQ) with changes in dose. We varied the time-current product within a range of clinically used values (40-140 mAs, corresponding to 3.5-12.4 mGy entrance dose and detector dose of 32-110 µGy). For the ACR phantom, the examined parameter was the number of detected objects. With the CDMAM phantom we chose the diameters 0.10, 0.13, 0.20, 0.31 and 0.5 mm and recorded the threshold thicknesses. With respect to the third method, we evaluated the NEQ at typical spatial frequencies to calculate the relative changes in NEQ. Plotting NEQ versus dose increment shows a linear relationship and can be described by a linear function (with R > 0.99). Every manually selectable current- time product increment can be detected. With the ACR phantom, the number of detected objects increases only in the lower dose range and reaches saturation at about 9 mGy entrance dose (80 µGy detector dose). The CDMAM can detect a 50% increase in dose over the examined dose range with all five diameters, although the increases of threshold thickness are not monotonous. We conclude that an NEQ-based method has the potential to replace the established detail phantom methods to detect dose changes in the course of QA.

[Intrathoracic dislocation fracture of the head of the humerus]. / Fracture-luxation intrathoracique de la tête humérale.

We present a rare case of fracture-dislocation of shoulder with intrathoracic displacement of the humeral head. This case is well documented by CT. The mechanism and treatment modalities are discussed, and pertinent literature is reviewed.

Growth hormone therapy with three dosage regimens in children with idiopathic short stature. European Study Group Participating Investigators.

OBJECTIVE: In children with idiopathic short stature (ISS) we studied the growth-promoting effect at 4 years of recombinant human growth hormone (rhGH) therapy in three dose regimens and evaluated whether increasing the dosage after the first year could prevent a decline in height velocity (HV). DESIGN: Included were 223 patients who were treated with subcutaneous administrations of rhGH 6 days per week. They were randomized to three groups: 3 IU/m2 body surface/day, 4.5 IU/m2/day, and 3 IU/m2/day during the first year and 4.5 IU/m2/day thereafter, corresponding with dosages of 0.2 and 0.3 mg/kg body weight/week, respectively. Growth was compared with a standard of 229 untreated children with ISS [ISS standard]. RESULTS: During the first year of treatment HV almost doubled and was higher with 4.5 IU/m2 than with 3 IU/m2. In the second year HV no longer differed among the groups, but increasing the dosage slowed the rate of the fall of HV. During 4 years of therapy the height SD score for age increased by a mean (SD) of 2.5 (1.0) [ISS standards], or 1.2 (0.7) (British standards), bone age increased by 4.8 (1.3) years, and predicted adult height SD score increased by 1.5 (0.7). After 4 years the results of the group with 4.5 IU/m2 were slightly better than those of the other groups. When dropouts were included in the analysis (assuming a stable height SD score after discontinuation of rhGH therapy), height gain was still significant. CONCLUSIONS: During 4 years of rhGH therapy, growth and final height prognosis improved, slightly more with 4.5 IU/m2 than with 3 IU/m2 or 3 to 4.5 IU/m2. However, bone age advanced on average 4.8 years during this period; therefore, any effect on final height will probably be modest.

[Aseptic osteonecrosis of the femoral condyle after meniscectomy by the arthroscopic approach]. / Ostéonécrose aseptique du condyle fémoral après méniscectomie par voie arthroscopique.

Retrospective review of 10 patients who presented with avascular necrosis of the ipsilateral femoral condyle following arthroscopic meniscectomy (9 medial, 1 lateral). The bone lesions were evaluated by radiography and MRI, which were repeated for few patients. MRI allows earlier diagnosis of avascular necrosis of the femoral condyle and offers an evaluation of extent of the lesions whose evolution is variable: 3 patients required a knee prothesis, the other 7 patients were treated medically.

Relationship between caries and level of metabolic balance in children and adolescents with insulin-dependent diabetes mellitus.

The relationship between the occurrence of caries and diabetes was explored in 80 children and adolescents with insulin-dependent diabetes mellitus. The mean age of the subjects was 14.5 years (range 11.7-18.4 years) and duration of diabetes 0.3-15.0 years (mean 6.0 years). DFS indices in poorly controlled subjects (glycosylated haemoglobin, HbA1, values over 13%) were significantly higher than in moderately (HbA1 10.0-12.9%) or in well-controlled cases (HbA1 values < 10%). However, the difference was not statistically significant if adjustments were made for age, age at the onset of diabetes and duration of diabetes (p = 0.1, Ancova). Subjects with caries and/or fillings had significantly higher short- and long-term HbA1 values than subjects with intact teeth, both if all subjects or subjects with long-term disease (duration of diabetes of at least 2 years, n = 62) were included. This finding was valid after adjustments for age, duration of diabetes and age at the onset of diabetes. Association between poor control and the loss of intact dentition was also demonstrated in subjects whose diabetes was diagnosed before the age of 7. Presence of yeasts was highly associated with poor control of diabetes, and yeasts were more frequently found in the saliva samples of subjects with decayed and/or filled teeth. Instead, salivary flow rates, salivary lactobacilli and Streptococcus mutans counts, buffering capacity and pH were not different between the subjects. As well, home care practices were similar, and all subjects had received similar regular dental treatment. In conclusion, poor control of diabetes was found to be associated with caries. The presence of yeasts may be a caries risk indicator in subjects with diabetes, since diabetes may enhance yeast growth, particularly if poorly controlled.

Collagen metabolites in the prediction of response to GH therapy in short children.

To evaluate the role of collagen metabolites in the prediction of the response to GH treatment we measured the serum concentrations of the C-terminal propeptide of type I procollagen (PICP) and the N-terminal propeptide of type III procollagen (PIIINP) with specific RIAs in 35 short children (16 boys) before and after 5 days, 5 weeks and 3 months of GH therapy. The mean age of the children was 10.3 years (range 1.9-16.4 years) and the bone age ranged from 1.2 to 12.5 years (mean 7.6 years). The initial mean relative height (RH) was -3.6 SDS (range -6.6 to -2.4 S.D.). Nineteen children were found to have GH deficiency (GHD; peak GH responses in two pharmacological tests < 10 micrograms/l), while the remaining 16 were considered to have undefined short stature (USS). The children were treated with recombinant human GH (0.1 U/kg given subcutaneously at bedtime 6-7 times/week). The increases in RHI over the first 6 and 12 months of therapy were used as response measures. There was already a significant increase (P < 0.001) in both the serum PICP and PIIINP levels at 5 days, and the concentrations continued to rise up to 3 months, PICP levels rising less than the PIIINP levels. In the whole group the RHI over 6 months correlated most strongly with the absolute PICP concentrations at 3 months (rS = 0.59; P < 0.05), while the absolute PIIINP concentrations at 3 months showed the strongest relation to the one year RHI (rS = 0.69; P < 0.001). In the GHD group the 6 month RHI was most strongly related to the absolute PICP concentration at 3 months (rS = 0.59; P < 0.05). In the USS group the absolute PICP concentrations at 3 months correlated most strongly with the one year RHI (rS = 0.82; P < 0.01). Significant correlations were also observed between the absolute PIIINP levels at 3 months and the 6 month RHI (rS = 0.60; P < 0.05) and 12 month RHI (rS = 0.76; P < 0.01) in this group. These results show that GH therapy results in an unequivocal increase in circulating concentrations of PICP and PIIINP. The serum PICP and PIIINP concentrations may be of value in the prediction of the long-term response to GH therapy.

Salivary factors in children and adolescents with insulin-dependent diabetes mellitus.

To determine whether hyperglycemia in IDDM (insulin-dependent diabetes mellitus) could interfere with salivary secretion rates, salivary glucose levels, and salivary microbial counts, we studied salivary factors in two groups of children and adolescents with IDDM. One study group included 14 children with newly diagnosed IDDM )mean age 11 years, SD +/- 2.4 years). Samples of saliva were collected on admission to hospital and after 2 weeks on insulin treatment. The other study group were 50 IDDM children (mean age 14.4 years, SD +/- 1.7 years, mean duration of diabetes 6.2 years, SD +/- 1.4 years) visiting the outpatient diabetic clinic. Samples of saliva were collected during two visits, approximately 3 months apart. In the newly diagnosed IDDM cases, mean salivary glucose level decreased from 54.1 +/- 31.7 mg/l to 35.2 +/- 29.5 mg/l (P = 0.096) after beginning insulin treatment. During hyperglycemia, salivary glucose levels correlated with mean blood glucose levels for the day concerned (r = 0.65, P < 0.05). The results suggest that high blood glucose levels can increase salivary glucose levels. Stimulated saliva secretion increased significantly from 5.4 +/- 3.3 ml/5 min to 7.3 +/- 2.6 ml/5 min (P < 0.01) while glucose balance improved. In the long-term IDDM cases, salivary flow rates and salivary glucose levels were not significantly related to the glycosylated hemoglobin (HbA1) values. Salivary glucose levels and salivary secretion rates were inversely correlated (P < 0.05). In conclusion, hyperglycemia was observed to be associated with decreased salivary secretion and high salivary glucose levels. As a consequence, salivary lactobacilli and yeast counts tended to increase.

A prospective, longitudinal study examining the development of retinopathy in children with diabetes.

A prospective longitudinal study of 182 children and adolescents with diabetes revealed that during a follow-up of 2.5 +/- 0.5 years the prevalence of retinopathy increased from 10.8% to 28.0%, corresponding to an annual increase of 7%. Retinopathy was diagnosed at a mean age of 15.3 years (95% CI, 14.8-15.8 years) after a mean duration of diabetes of 8.9 years (95% CI, 8.0-9.7 years). Prepubertal years of diabetes contributed to the risk of developing retinopathy. The initial signs of retinopathy were microaneurysm(s) in 56%, microaneurysm(s) and haemorrhage(s) in 30%, and haemorrhage(s) in 10%. A combination of microaneurysm, haemorrhage and cotton-wool spot was observed in 2%, and microaneurysms, haemorrhage and an IRMA lesion were seen in 2%. Most of the initial lesions disappeared during the follow-up period, but at the same time new lesions developed elsewhere in the retina in all but 2 cases. In 8 patients (15% of patients with retinopathy) aged 13.7-19.8 years and having had diabetes for 3.7-14.8 years, retinal changes progressed from mild to a more advanced background retinopathy. A higher glycated haemoglobin level during puberty was the only factor which differentiated these patients from control patients matched for sex, age, puberty and duration of diabetes.

Normal stimulated growth hormone secretion but low peripheral levels of insulin-like growth factor I in prepubertal children with insulin-dependent diabetes mellitus.

The hypothalamo-pituitary-insulin-like growth factor I (IGF-I) axis was studied in 24 prepubertal children with insulin-dependent diabetes mellitus (IDDM) and 12 non-diabetic children. There were no significant differences between the diabetic and control subjects in basal concentrations of immunoreactive growth hormone releasing hormone (ir-GHRH), growth hormone (GH) or stimulated GH levels, but after exercise ir-GHRH concentrations were higher in the diabetic children. Peripheral IGF-I levels were significantly lower in the diabetic children, and even lower in those with poor metabolic control. A positive correlation was found between IGF-I levels and circulating free insulin concentrations in the diabetic subjects (r = 0.49, p < 0.05). These observations suggest that the GH response to physiological stimulation is normal in prepubertal diabetic children. Exercise-induced GH response may not be mediated by GHRH. IGF-I levels were reduced in prepubertal children with IDDM and even more so in subjects with poor metabolic control. This may be a consequence of transitory hypoinsulineamia, emphasizing the importance of adequate insulinization to facilitate optimal growth in children and adolescents with IDDM.

Defective stimulation of adipocyte adenylate cyclase, blunted lipolysis, and obesity in pseudohypoparathyroidism 1a.

Adipocyte plasma membranes were isolated from four patients with type 1a pseudohypoparathyroidism, a disease in which deficiency of the stimulatory guanine nucleotide binding protein Gs has been reported, and from controls. Stimulation of adenylate cyclase by isoproterenol was defective, whereas inhibition of forskolin-stimulated cyclase activity by N6-(phenylisopropyl)adenosine was normal. The patients had low serum FFA concentrations and developed obesity in childhood. These results suggest that pseudohypoparathyroidism 1a is connected with a blunted stimulatory response of adenylate cyclase, possibly because of low Gs activity, and that this blunted response may lead to decreased lipolysis and to obesity.

Prevalence and risk factors of retinopathy in children with diabetes. A population-based study on Finnish children.

The prevalence of retinopathy in children with insulin-dependent diabetes mellitus (IDDM) was studied in a population-based survey on 194 of the 216 subjects (89.8%) with IDDM aged 4.6 to 16.6 years living in the county of Oulu, Finland. The diagnosis of retinopathy was based on fundus photography. The median age of the children was 12.2 years and the median duration of diabetes 4.5 years (range 0.14.2 years). Retinopathy was found in 21 (10.8%) of cases. All of the changes seen were mild and did not require treatment. All the children with retinopathy were pubertal or postpubertal, and an association was found between the presence of retinopathy and the long-term diabetes control, duration of diabetes, age and albuminuria. Logistic regression analysis showed increasing duration of diabetes, puberty and elevated blood glycated haemoglobin to be the main risk factors explaining the occurrence of retinopathy. In patients aged 13-16 years retinopathy was also related to female sex and diastolic blood pressure, but in logistic regression analysis duration of diabetes and glycated haemoglobin were the best predictors.

Clinical characteristics and circulating collagen and laminin metabolites in insulin-dependent diabetic children with joint and skin manifestations.

One hundred seventy-four children and adolescents with insulin-dependent diabetes mellitus were examined for joint contractures and skin manifestations in their hands. Joint contractures were found in 52 (29.8%) and skin manifestations in 29 (16.6%) patients. To eliminate the possible confounding effects of age and duration of diabetes on the variables to be studied, patients younger than 7 y and with a duration of diabetes shorter than 3 y were excluded from the subsequent analyses. Of the remaining 108 children, those with joint contractures had lower serum concentrations of the 7-S domain of type IV collagen and the P1 fragment of laminin than the other patients (p = 0.033) but higher mean glycated Hb levels (p = 0.048). A clear association was noted between the occurrence of joint contractures and skin changes (p = 0.007). Background retinopathy was found in six patients (5.6%), three of whom had stage II joint contractures (p = 0.064). The children with skin changes and those with combined joint and skin manifestations more often had insulin-dependent diabetes mellitus in their first-degree relatives (p = 0.038 and p = 0.043, respectively). No difference in relative height was found between the groups. No association could be seen between disease susceptibility antigens in the HLA-D locus and joint or skin manifestations. The lower levels of circulating collagen and laminin metabolites in the diabetic children with joint contractures suggest that these patients are characterized by a reduced turnover of basement membranes in tissues.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of conventional dose growth hormone therapy for two years on height velocity and height prognosis in girls with Turner syndrome.

The aims of this national multicentre study in Finland were to evaluate whether the height velocity of patients with Turner syndrome would increase with the conventional human growth hormone (GH) therapy regimen normally given to GH-deficient children and whether girls with Turner syndrome actually show GH neurosecretory dysfunction. Finally, the study should show whether GH therapy improves height prognosis and, eventually, final height. Twenty-five girls with Turner syndrome, aged 7.5-14.4 years, entered the study. Their ability to secrete GH was determined and, surprisingly, several would have been classified as having GH deficiency. All girls received GH, 0.1 IU/kg/day (maximum dose 4 IU/day) s.c., and once over 12.5 years old, they also received oestradiol valerate and fluoxymesterone. They showed a convincing increase in height velocity, and rapid growth continued during the second year of therapy. The effect of GH therapy on final height is still unknown. The therapy was remarkably free of side-effects.

Normal C3b receptor (CR1) genomic polymorphism in patients with insulin-dependent diabetes mellitus (IDDM): is the low erythrocyte CR1 expression an acquired phenomenon?

Expression of the erythrocyte complement receptor (C3bR = CR1 = CD35) and its genomic polymorphism (HindIII RFLP) was studied in a group of 80 patients with IDDM, 31 healthy siblings and 101 healthy blood donors. Defective CR1 expression was found in 26% of the patients with IDDM compared with 9% of the controls (P less than 0.05) and 0% of the siblings. The CR1 gene polymorphism of the IDDM patients did not significantly differ from that of the controls. The presence of a 6.9 kb (L) CR1 gene fragment was associated with a low CR1 expression in the patients (P less than 0.05) and especially in the controls (P less than 0.001). No significant association was found between the presence or absence of the HLA risk antigens for IDDM and CR1 expression. The results confirm that erythrocyte CR1 expression is genetically determined, but the CR1 deficiency associated with IDDM seems to be an acquired rather than a genetic phenomenon.

Abnormalities within CD4 and CD8 T lymphocytes subsets in type 1 (insulin-dependent) diabetes.

Abnormalities in the proportions of various T lymphocyte subpopulations have been found in a number of autoimmune diseases. Monoclonal antibodies labelled with various fluorochromes were used here to define the percentages of subsets, and especially to divide CD4+ (helper/inducer) and CD8+ (suppressor/cytotoxic) cells into phenotypic subgroups. Blood samples were analysed from 25 patients (age 10.1 +/- 3.7 years) with recently diagnosed insulin-dependent diabetes mellitus (IDDM) and 25 age- and sex-matched control subjects. The percentages of CD4+ cells and CD4+CD45RA+ cells described as naive T helper cells or suppressor/inducers were increased in the IDDM patients (P less than 0.05 and P less than 0.05. Student's t-test, respectively), whereas the percentage of CD4+CD45RA- cells (memory T-helper cells, helper/inducers) was similar in the patients and controls. The percentage of CD8+CD11b+ cells containing suppressor/effector lymphocytes was decreased in the IDDM patients as compared with the controls (P less than 0.01) but no significant difference was seen in total CD8+ cells. The percentages of CD3+ cells and the proportions of these simultaneously positive for HLA-DR antigen (activated T cells) were also increased in the recent IDDM patients (P less than 0.001 and P less than 0.05, respectively), while the proportion of CD20+ B cells was decreased (P less than 0.05). The findings support the view that disturbed immune regulation occurs in IDDM and indicate that further division of T cell subpopulations may clarify our understanding of the disease process.

Hereditary gingival fibromatosis associated with growth hormone deficiency.

A case report of gingival fibromatosis in association with growth hormone (GH) deficiency due to a lack of growth hormone releasing factor (GRF) is presented. The girl is the youngest member of a family of eight children, five of whom lack the same hormone and have or have had similar gingival enlargements. After the growth hormone deficiency had been diagnosed and hormone substitute administered the dental age of the girl presented came closer to that of her age and sex-matched controls but did not reach the corresponding values even though the teeth were exposed by excising the overgrown gingiva. Test fibroblasts cultured from the overgrown gingiva proliferated at a slower rate than those cultured from age-matched controls. Total RNA was extracted from the test and three control fibroblasts and examined by Northern hybridisation using cDNAs for pro alpha 1(I) and pro alpha 1(III) chains. The amount of type I and III procollagen mRNAs were lower in the test fibroblasts as compared to the controls.

Comparison of children with type 1 (insulin-dependent) diabetes in northern Finland and southern Ontario: differences at disease onset.

This study was undertaken to evaluate whether differences in Type 1 diabetes incidence in two separate geographical locations are associated with any differences in biochemical and immunological features at the onset of the disease. We studied all children under 16 years of age who presented at the time of diagnosis with Type 1 diabetes to the children's hospitals in Oulu (n = 43) and Toronto (n = 87) during 1984-1985. At onset children from Northern Finland had lower blood glucose and HbAlc levels, and higher C-peptide concentrations than those from Southern Ontario (p's less than 0.01). The group from Northern Finland also had a higher incidence of multiplex families (18.6 vs 4.6%, p less than 0.01). Amongst the Finnish group, those from multiplex families had a higher C-peptide concentration and lower frequency of ketoacidosis than those from simplex families (p's less than 0.05). Thus differences do exist at the onset of diabetes in these groups from geographical locations with greatly different incidences of Type 1 diabetes.