Imaging for local recurrence of breast cancer.

PURPOSE: Isolated locoregional recurrence of breast cancer (ILRR) and contralateral breast cancer (CBC) affect up to 20% of all breast cancer (BC) patients in the first 20 years after primary diagnosis. Treatment options comprise surgical interventions and further systemic therapies depending on the histological subtype. Patients with hereditary breast or ovarian cancer (HBOC) undergo MRI, mammography, and ultrasound in the aftercare of BC, while non-HBOC (nHBOC) patients do not regularly receive MRI. Since early detection is crucial for morbidity and mortality, the evaluation and constant improvement of imaging methods of the breast is necessary. METHODS: We retrospectively analyzed the data of 1499 former BC patients that received imaging of the breast at a tertiary-care university hospital between 2015 and 2020. The analysis comprised various patient characteristics, such as breast density, age, tumor size and subtype, and their influence on BC detection rates by the different imaging methods. RESULTS: Within the patient sample, 176 individuals (11.7% of former BC patients) were diagnosed with either ILRR or CBC. CBC was observed in 32.4% of patients, while both ILRR and secondary breast cancer occurred in 20.5% and 23.9% of all patients. Sensitivity of MRI, mammography, and ultrasound for recurrent malignancy was 97.9%, 66.3%, and 67.8%, respectively. ILRR and CBC detection rates were similar for patients with and without HBOC history. Lower breast density and larger tumor size increased the detection rates of all imaging modalities. CONCLUSION: In breast cancer survivors, MRI might improve the early detection of ILRR and CBC in both HBOC and nHBOC patients.

Approaching the Gamow Window with Stored Ions: Direct Measurement of

We report the first measurement of low-energy proton-capture cross sections of ^{124}Xe in a heavy-ion storage ring. ^{124}Xe^{54+} ions of five different beam energies between 5.5 and 8 AMeV were stored to collide with a windowless hydrogen target. The ^{125}Cs reaction products were directly detected. The interaction energies are located on the high energy tail of the Gamow window for hot, explosive scenarios such as supernovae and x-ray binaries. The results serve as an important test of predicted astrophysical reaction rates in this mass range. Good agreement in the prediction of the astrophysically important proton width at low energy is found, with only a 30% difference between measurement and theory. Larger deviations are found above the neutron emission threshold, where also neutron and γ widths significantly impact the cross sections. The newly established experimental method is a very powerful tool to investigate nuclear reactions on rare ion beams at low center-of-mass energies.

[Treatment of homozygous familial hypercholesterolemia with LDL-apheresis on a 4-year-old child]. / Traitement d'une hypercholestérolémie familiale homozygote par LDL-aphérèse chez un enfant de 4 ans.

Homozygous familial hypercholesterolemia (HFH) is a rare genetic disease associated with increased atherosclerosis, resulting in premature death near the age of 20 years. Treatment requires the LDL-apheresis system. M, born from a consanguineous union, suffers from HFH (total-cholesterol=12.29 g/l, LDL-cholesterol=9.65 g/l). Diet and drug treatment was not associated with decreased LDL-cholesterol. At the age of 4.5 years (body weight: 16.7 kg), M began treatment with LDL-apheresis. Apheresis treatment was given every 2 weeks using the Direct Adsorption of LIpoprotein (DALI system, a process that involves total-blood filtration. During the first 26 sessions, the mean reduction in LDL-cholesterol was 67+/-12%, while HDL-cholesterol decreased by only 17+/-11%. Mean LDL-cholesterol concentration decreased from 6.54+/-0.93 g/l (before apheresis) to 2.21+/-0.95 g/l (after apheresis). Apart from iron deficiency anemia, no major side effects were observed. LDL-apheresis using the DALI system is associated with significant reductions in LDL-cholesterol (similar to reports from the literature) without major side effects, even in a child weighing less than 20 kg. A long term, multinational (European) study is needed to confirm these results.

[Severe Stevens-Johnson syndrome in 4 children]. / Syndrome de Stevens-Johnson sévère chez l'enfant: à propos de 4 observations.

Stevens-Johnson syndrome is an acute, self-limiting disease of the skin and mucous membranes. Erythema multiforme, Stevens-Johnson syndrome and toxic epidermal necrolysis are all part of a single spectrum illness. We report severe erythema multiform in 4 children aged from 6 to 15 years old. Erythema was mostly related to mycoplasma pneumoniae infection (3/4) and 1 case was attributed to drugs. Two children developed severe sequelae (obliterans bronchiolitis). No patient had recurrent disease. The early use of steroids is still debated, but in our experience it seems to benefit overall. A long term follow-up is necessary with the study of pulmonary function tests and chest X-rays ophtalmologic and dermatologic examination.

Lung disease in ataxia-telangiectasia.

UNLABELLED: Ataxia-telangiectasia (AT) is a multi-systemic disease caused by mutational inactivation of the ATM gene. We report a retrospective study of lung disease in 15 patients. PATIENTS AND METHODS: A diagnosis of AT was made if the patient met the following criteria: neurological features and at least one the following: oculo-cutaneous telangiectasia, elevated serum alpha-feto-protein level. RESULTS: Recurrent sino-pulmonary infections were usually present in 11 of the cases and occurred during the first 2 years of life. Other lung injuries noted were bronchiectasis, obstruction and restriction of the airways, fibrosis, pneumothorax and haemoptysis. Eleven children had immunodeficiencies. DISCUSSION: Recurrent sino-pulmonary manifestations precede neurological complications, but the severity of neuro-degeneration and pulmonary disease were not correlated. Pulmonary status was a prognosis factor. Immunodeficiency was the main, but not the only, aetiology for lung disease in AT. CONCLUSION: There is little dispute over the role of ATM in lung and respiratory epithelium. To reduce the morbidity associated with AT, there needs to be greater awareness of respiratory complications. Early management and monitoring lung function is necessary to minimize lung damage.

Comparison of resting energy expenditure in bronchopulmonary dysplasia to predicted equation.

OBJECTIVE: Children with bronchopulmonary dysplasia (BPD) often suffer from growth failure because of disturbances in energy balance with an increase of resting energy expenditure (REE). Evaluation of REE is a useful tool for nutritional management. Indirect calorimetry is an elective method for measuring REE, but it is time consuming and requires rigorous procedure. The objective of this study was to test accuracy of prediction equation to evaluate REE in BPD children. PATIENTS AND METHODS: Fifty-two children aged 4-10 years with BPD (30 boys and 22 girls) and 30 healthy lean children (20 boys and 10 girls) were enrolled. In this study, indirect calorimetry was compared to four prediction equations (Schoffield-W, Schoffield-HW, Harris-Benedict and Food and Agriculture Organization equation) using Bland-Altman pair wise comparison. RESULTS: The Harris-Benedict equation was the best equation to predict REE in children with BPD, and Schoffield-W was the best in healthy children. For the children with chronic lung disease of prematurity the Harris-Benedict equation showed the lowest mean predicted REE-REE measured by indirect calorimetry difference (difference = 15 kcal/day; limits of agreement -266 and 236 kcal/day; 95% confidence interval for the bias -207 to 177 kcal/day), and graphically, the best agreement. For the group of healthy children, it was the Schofield-W equation (-2.9 kcal/day; limits of agreement -275 and 269 kcal/day; 95% confidence interval for the bias -171 to 165 kcal/day), and graphically, the best agreement. CONCLUSION: Differences in prediction equation are minimal compared to calorimetry. Prediction equation could be useful in the management of children with BPD.

Body composition in children with bronchopulmonary dysplasia predicted from bioelectric impedance and anthropometric variables: comparison with a reference dual X-ray absorptiometry.

UNLABELLED: Since children with bronchopulmonary dysplasia often suffer from malnutrition and growth failure, evaluation of body composition is a very important tool to nutritional support. The aim of this study was to compare assessment of fat-mass (FM) and fat-free mass (FFM), evaluated by bio-impedancemetry and anthropometry compared to dual-X-ray-absorptiometry (DXA) in children with bronchopulmonary dysplasia. PATIENTS: Seventy-one children, aged 4-8 years, with bronchopulmonary dysplasia were enrolled. METHODS: FM and FFM measured using anthropometry and bio-impedancemetry were compared to FM and FFM obtained by DXA using the Bland-Altman method. RESULTS: Both bio-impedancemetry and anthropometry gave good agreement with DXA to evaluate FM and FFM. Anthropometry method, in general, slightly under-estimated FM (mean difference: -0.02 kg, standard deviation: 0.99) and FFM (mean difference: -0.70 kg+/-1.72). Bio-impedancemetry method overestimated FM (mean difference: 0.34 kg+/-2.06) and underestimated FFM (mean difference: -1.24 kg+/-3.32). CONCLUSION: In children with bronchopulmonary dysplasia aged, 4-8 years, both anthropometry and bio-impedancemetry cannot be used to precisely evaluate body composition.

[Ataxia-telangiectasia: a review]. / Ataxie-télangiectasie: de la clinique à la physiopathologie.

Ataxia-telangiectasia (AT) is an autosomal recessive inherited disease caused by mutational inactivation of the ATM gene. It is a multisystemic disease, characterized by progressive neurological dysfunction, especially in the cerebellum, oculo-cutaneous telangiectasia, immunodeficiency, recurrent sino-pulmonary infections and high incidence of neoplasms. The responsible gene, ATM, encodes a large protein that belongs to a family of protein kinases with a phosphatidylinositol 3-kinase (Pi3K) domain. ATM is a key regulator of cell cycle checkpoints that causes DNA repair or apoptosis. Several studies report ATM function in target cells (such as neurons, fibroblast, endothelium, germ cells, lymphocytes). The pleiotropic phenotypes of AT reflect the multifaceted activities of ATM protein. In nucleus (lymphocytes, fibroblasts, germ cells) ATM is involved in regulation of cell-cycle checkpoints; in cytoplasm ATM regulates redox state (neurons).

Congenital idiopathic intestinal pseudo-obstruction and hydrocephalus with stenosis of the aqueduct of sylvius.

We present the first report of an association between hydrocephalus with stenosis of the aqueduct of Sylvius (HSAS) and a specific form of congenital idiopathic intestinal pseudo-obstruction (CIIP) in an infant. Diagnosis of HSAS was suspected during the neonatal period because of a severely dilated ventricular system associated with bilateral adducted thumbs, and was confirmed by demonstration of a mutation in the gene encoding L1 cell adhesion molecule (L1CAM). L1CAM mutations cause a variable clinical spectrum. This gene is located at Xq28 and encodes a transmembrane glycoprotein involved in neurite outgrowth and neuronal migration. Hirschprung disease has been reported to involve an L1CAM mutation that manifests as a quantitative defect in the migration of neural crest cells in distal segments of the gut. We report an association that suggests that alterations of L1CAM may cause another type of intestinal pseudo-obstruction distension with a qualitative defect in differentiated Cajal's cells in the anterior part of the gut. This observation suggests that L1CAM has a role in the developmental regulation of multiple systems. Further clinical descriptions of gastroenterological and neuropathological data are required to extend our understanding of the mechanisms underlying L1CAM functions.

[Nutrition and bronchopulmonary dysplasia]. / Nutrition et dysplasie bronchopulmonaire.

Bronchopulmonary dysplasia remains a frequent complication of extreme prematurity. In preterm neonates catch-up and pulmonary alveolar growth occur during the first two years of life. However 10 to 25% of preterm infants with bronchopulmonary dysplasia are under-nourished after two years of age, and 30 to 60% of them also suffer from persistent airway obstruction, hyperinflation and bronchial hyperreactivity. Recommendations on nutritional requirements in this population are not yet clearly defined, but an adequate nutritional status in prenatal and early postnatal period can have long-term consequences on brain and lung development. There are a few randomised trial of nutrition for preterm infants with bronchopulmonary dysplasia after discharge. Caloric and protein requirements in this population are probably higher than in full-term infants. Moreover there are potential benefits in using specific nutrients: supplementation with long chain polyunsaturated fatty acids could decrease lung inflammation injuries, glutamine is the main source of energy of pneumocyte, vitamin A is essential for lung development, inositol is necessary for surfactant synthesis, vitamin E and selenium have anti-oxidant effects. Controlled nutritional trial are needed with a long term follow-up in late childhood in order to test their effects on growth and pulmonary status.

[Perforated gastric ulcer in the child: a rare complication, a case report]. / Perforation d'ulcère gastrique de l'enfant: une complication rare, à propos d'un cas.

UNLABELLED: Perforated gastric ulcer is unusual in children. We report a case in a girl with an unexpected evolution. CASE REPORT: A 13-year-old girl was admitted for abdominal pain. She had no particular personal history but her father had a perforated ulcer. On admission she was not painful, her abdomen was soft on palpation. The white blood cell count was 1.7 x 10(3)/mm3. A right pneumoperitoneum was seen on an abdominal X-ray film. Because of her good general status and the normalization of the abdominal X ray film six hours later, no surgical exploration was performed. On the fourth day, a gastrointestinal endoscopy showed an anterior gastric ulcer which was perforated. Biopsies did not isolate H. pylori. The patient was given a treatment with amoxicillin-metronidazole (7 d) and oméprazole (7 weeks). An endoscopic control, one month later, showed a total healing of the gastric ulcer. CONCLUSION: Peptic ulcerations and their complications are underdiagnosed in childhood. This could lead to delay in diagnosis or inappropriate treatment specially in case of perforation.

Contamination of gastrostomy feeding systems in children in a home-based enteral nutrition program.

BACKGROUND: There are few data concerning the risk of contamination of enteral feeding systems via gastrostomy in children, and none for conditions that pertain to home-based care. METHODS: To investigate the risk of contamination of enteral feeding systems during the home-based care of 20 children receiving gastrostomy tube feeding, five samples were taken for analysis: two samples before the enteral feeding period (gastrostomy, enteral feeding system) and three after this period (gastrostomy, distal giving set, liquid remained in container). Microorganisms were identified and counted. Different factors were studied to elucidate their role in bacterial colonization: acid suppressive therapy, gastrostomy tube or button, hanging feeding time, rate of enteral feeding, gastric pullulation and retrograde contamination, manipulation error, and use of open or closed enteral feeding systems. RESULTS: Overgrowth was defined as a microorganismal load exceeding 10(4) colony-forming units (cfu)/mL. Overgrowth was present in 85% of gastrostomy samples before enteral nutrition started. Most microorganisms belonged to gastric flora. Some bacteria had an environmental origin or derived from cutaneous flora. Forty-five percent of the lines showed overgrowth at the end of enteral nutrition period, mainly with the same microorganism found in the gastrostomy. Closed enteral bags remained sterile, even if manipulation error occurred. Duration, rate of enteral feeding, and acid suppression treatment were not risk factors for overgrowth. CONCLUSIONS: Retrograde contamination of gastrostomy feeding systems occurs frequently. The preferential use of closed enteral feeding systems is recommended for home-based enteral nutrition programs.

Incidence of multiglandular disease in primary hyperparathyroidism determined by parathyroid hormone secretion.

BACKGROUND: Successful parathyroidectomy depends on recognition and excision of all hyperfunctioning parathyroid glands. Because histologic definition is limited, multiglandular disease (MGD) is usually determined grossly by means of estimation of gland size and the experience of the surgeon, resulting in frequency varying from 8% to 33%. Normalization of elevated intraoperative intact parathyroid hormone (iPTH) levels after excision of all hyperfunctioning glands is necessary for postoperative normocalcemia and indicates normal secretion of remaining parathyroids. Abnormal hormone secretion measured during operation has been used to define the extent of excision and the incidence of MGD. METHODS: One hundred ten consecutive parathyroidectomy patients with no previous neck surgery or history of multiple endocrine neoplasia had intraoperative iPTH assays performed before and after excision of any suspected abnormal parathyroid gland(s). A drop in iPTH level after gland excision predicted postoperative normal calcium levels. RESULTS: All patients except one had normalization of serum calcium levels (average follow-up, 15 months). One hundred five patients had only one hyperfunctioning gland removed, and all have remained normocalcemic. Five (5%) patients had more than one gland involved: four had two or more hyperfunctioning parathyroids and one patient, who had a large parathyroid cyst removed, remained hypercalcemic. CONCLUSIONS: By using a biochemical assay, instead of estimated size, to predict which parathyroid glands are hypersecreting, the incidence of MGD in primary hyperparathyroidism was found to be 5%.

Inhibitory effects of recombinant human interleukin 10 on disease manifestations in a P-->F1 model of acute graft versus host disease.

Interleukin 10 (IL-10) is a cytokine with both antiinflammatory and immunosuppressive properties. In the present study, we have examined the effects of recombinant human IL-10 (rHuIL-10) on the development of acute graft-vs.-host disease (GVHD) in unirradiated (C57B1/6JxA/J) F1 recipients of parental A/J lymphocytes. rHuIL-10 (2.5 to 100 micrograms/mouse administered subcutaneously) caused a significant reduction in splenomegaly in GVH mice. GVH splenocytes exhibited an augmented capacity to produce IFN-gamma when stimulated in culture with Con A or LPS. The IFN gamma produced in response to LPS stimulation was found to be derived from CD4+ and CD8+ T cells with little or no contribution from the NK1.1+ subpopulation of the GVH spleen. Treatment with IL-10 in vivo was found to diminish the capacity of splenocytes to produce IFN gamma when stimulated with LPS but not with Con A. IL-10 did not protect GVH mice from a lethal dose of LPS but caused a marked reduction in the serum TNF alpha response triggered by the LPS challenge. We conclude that IL-10 may be useful in controlling those clinical manifestations of acute GVHD that arise as a result of the activities of proinflammatory cytokines such as IFN gamma and TNF alpha.

The cooperative effects of TNF-alpha and IFN-gamma are determining factors in the ability of IL-10 to protect mice from lethal endotoxemia.

Recent studies have demonstrated that interleukin-10 (IL-10) has the capacity to protect mice from the lethal effects of endotoxin. In this investigation, we have examined the ability of IL-10 to protect both normal mice and Corynebacterium parvum-primed mice against endotoxin lethality. In the overwhelming majority of experiments, recombinant murine IL-10 (rMuIL-10) and recombinant human IL-10 (rHuIL-10) did not protect normal BALB/cJ mice from lipopolysaccharide (LPS)-induced lethality at doses up to 10 micrograms/mouse. Despite their inability to protect, both IL-10 preparations were highly effective in preventing the increase in serum tumor necrosis factor alpha (TNF-alpha) that occurred in response to the lethal dose of LPS. Moreover, a neutralizing antibody against TNF-alpha gave only partial protection when administered alone to BALB/cJ mice. Treatment with a combination of neutralizing antibodies against TNF-alpha and interferon-gamma (IFN-gamma) resulted in complete protection. In contrast to BALB/cJ mice, normal BDF1 mice were protected from lethal endotoxemia by treatment with both rMuIL-10 and rHuIL-10. However, IL-10 did not protect C. parvum-primed BDF1 against LPS lethality even though it caused a reduction in the LPS-induced serum TNF-alpha response in C. parvum-primed mice as well as in normal BDF1 mice. Neutralizing antibodies against TNF-alpha and IFN-gamma were protective when administered alone to normal BDF1 mice, as previously demonstrated in C. parvum-primed mice. These findings suggest that lethal endotoxemia is a result of the cooperative activities of TNF-alpha and IFN-gamma in normal mice of the BALB/cJ and BDF1 strains as well as in C. parvum-primed BDF1 mice. IL-10 appears to be less effective in protecting mice from lethal endotoxemia when cooperation between IFN-gamma and TNF-alpha is facilitated by high-level production of the cytokines as in C. parvum-primed mice or when there is evidence of strong synergy between them as in normal BALB/cJ mice.

Lipopolysaccharide-induced cytokine production and mortality in mice treated with Corynebacterium parvum.

Tumor necrosis factor alpha (TNF-alpha) has been shown to be an important mediator of the lethal effects of endotoxin in several experimental models of septic shock. However, studies with a recombinant human interleukin-1 (IL-1) receptor antagonist protein (IL-1ra) suggest a role for IL-1 as a mediator of septic shock as well. In the present study, we show that mice treated in vivo with Corynebacterium parvum are primed for the production of interferon-gamma (IFN-gamma) and exhibit an enhanced capacity to produce serum IL-1 alpha, TNF-alpha, and IL-6 when challenged intravenously with lipopolysaccharide (LPS). The majority of C. parvum-treated mice die within 24 h of an LPS challenge. Pretreatment with a rat antimouse TNF-alpha monoclonal antibody (mAb) protected 90% of the animals against the lethal endotoxin challenge, while an anti-IFN-gamma mAb gave approximately 75% protection. The anti-IFN-gamma mAb also caused a reduction in LPS-induced serum TNF-alpha and IL-1 alpha. Anti-IL-1 alpha, anti-IL-1 beta, and anti-IL-6 neutralizing mAb did not protect against lethality when administered to mice prior to the LPS challenge. These results indicate that TNF-alpha and IFN-gamma are major mediators of endotoxin shock in C. parvum-treated mice. The results further suggest that the IFN-gamma produced by C. parvum-primed mice in response to an LPS challenge serves as a stimulus for enhanced production of TNF-alpha and IL-1 alpha. These findings are consistent with an increasing body of evidence suggesting a major role for IFN-gamma in lethal endotoxemia.

Sudden blindness and total ophthalmoplegia in mucormycosis. A clinicopathological correlation.

A case of rhino-orbitocerebral mucormycosis is presented, illustrating the serious nature of this disease. Clinical features and their pathological correlations are demonstrated. The need for a high index of clinical suspicion, and an early biopsy of the affected area is emphasized so that the benefits of early diagnosis and therapy may be gained.

A study of cytokine production in acute graft-vs-host disease.

The role of cytokines in the development of acute graft-vs-host disease (GVHD) was investigated in B6AF1 mice that were injected with parental A/J lymphocytes. Splenocytes from GVH mice exhibited an increased capacity to produce interleukin (IL)-1, IL-6, and TNF-a when stimulated in culture with lipopolysaccharide (LPS). This enhanced capacity was diminished following in vivo treatment with immunosuppressive drugs. Concanavalin A-stimulated GVH spleen cells produced significantly lower levels of IL-2 but higher levels of interferon-gamma (IFN-gamma) than did syngeneic spleen cells. Immunosuppressive therapy in vivo increased the capacity of GVH spleen cells to produce IL-2. However, immunosuppressants differed in their effects on IFN-gamma production. Sch 24937 (6-bromo-5-chloro-2-[1-(methylsulfonyl)acetyl] 3-(2-pyridyl)indole) enhanced or had no effect while cyclosporin A consistently decreased the capacity of splenocytes to produce this lymphokine. These results indicate that the capacity of GVH splenocytes for cytokine production can be differentially affected by the actions of some pharmacological agents. The data also indicate that there may be differential regulation of the production of IL-2 and IFN-gamma by the Th1 subset in the GVH spleen.