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Biomedical subjects

S Neuenschwander

Publications and source records attributed to S Neuenschwander.

At least 55 records · Page 3Linked to original sources

Outcome of residual mediastinal masses of thoracic lymphomas in children: impact on management and radiological follow-up strategy.

BACKGROUND: Following treatment with chemotherapy and radiotherapy, patients with thoracic lymphomas may demonstrate benign residual mediastinal masses, composed of inflammatory, fibrous or necrotic tissue. Because of the potential risk of viable tumour cells within the mass, histological verification of the nature of these masses may be requested. OBJECTIVE: To study the outcome of thoracic lymphomas in children in order to optimise the radiological follow-up strategy of residual mediastinal masses (RMM). MATERIALS AND METHODS: A retrospective study of 39 children [24 with Hodgkin's disease (HD), 10 with non-Hodgkin's lymphoma (NHL), and 5 with anaplastic lymphoma (AL)]. The results of chest X-rays (CXR) and thoracic CT performed at the time of re-assessment were compared with the histology of the residual masses (n = 11) or the clinical course (n = 28). RESULTS: At the time of re-evaluation, 16/39 patients had residual mediastinal enlargement (RME) on CXR, and 18/39 patients had RMM on CT. Good concordance was observed between the two imaging modalities (K = 0.69). Two children with a RMM died from extra-mediastinal progression. Two children with NHL had active residual mediastinal lesions but neither had RMM. Sixteen cases of RMM were observed in the remaining 35 children and 9 of these masses were histologically verified as benign. A favourable course was observed in these 35 cases. CONCLUSIONS: RMM are frequent and generally benign. They are well shown on CXR and have a non-specific appearance on CT. Except when required by a treatment protocol, they could be submitted to further radiological follow-up before contemplating surgical verification.

Child↗

Effects of neurohypophyseal hormone analogues on blood clotting factor VIII and fibrinolytic activity in sheep.

The increase in blood clotting factor VIII (antihaemophilic factor, F-VIII) and fibrinolytic activity induced by the administration of neurohypophyseal hormone analogues, was assayed in sheep. Peptides with high selectivity for vasopressin V1, V2 or myometrial oxytocin receptors in the dose range of 0.1-10 micrograms/kg body weight were investigated. The main conclusions are as follows. The time-course of the F-VIII plasma levels following the administration of the peptides was biphasic, with one surge at about 20 min, a rebound phase, and another increase with the maximum at 60-90 min. The time-course of the fibrinolytic response, expressed as biological activity of plasminogen activator in the plasma euglobulin fraction, displayed a single maximum within 60 min. The baseline responses were reached within 90-120 min. Responses were expressed as integrals of the time-concentration curves in a predetermined time range (90-120 min). F-VIII and plasminogen activator enhancing effects seemed to be tightly linked to the specific vasopressin V2 receptor activities. [Val4,D-Arg8]Vasopressin displayed higher plasminogen activator activities than the standard substance, deamino[D-Arg8]vasopressin. The vasotocin analogue [Phe2,Orn8]oxytocin, a specific vasopressin V1 receptor agonist, also displayed high antihaemophilic and fibrinolytic potencies, expressed in terms of ED50 values, but did not reach the same maximal response as vasopressin V2 receptor agonists. Oxytocin and its highly selective uterotonic analogue, [Thr4,Gly7]oxytocin, displayed low antihaemophilic, and virtually no plasminogen activating potencies. Surprisingly, vasopressin V2 and V1V2 receptor antagonists studied in our experiments showed both enhanced F-VIII and fibrinolytic responses. Dose-response curves frequently displayed a decrease of the F-VIII, and sometimes also decreased fibrinolytic responses, at higher peptide doses. Strong decreases of the packed cell volume (haematocrit) and somewhat lower decreases of the total plasma protein concentration were observed shortly after administration of the peptides.

Animals↗

Two alpha(1,2) fucosyltransferase genes on porcine chromosome 6q11 are closely linked to the blood group inhibitor (S) and Escherichia coli F18 receptor (ECF18R) loci.

The Escherichia coli F18 receptor locus (ECF18R) has been genetically mapped to the halothane linkage group on porcine Chromosome (Chr) 6. In an attempt to obtain candidate genes for this locus, we isolated 5 cosmids containing the alpha (1,2)fucosyltransferase genes FUT1, FUT2, and the pseudogene FUT2P from a porcine genomic library. Mapping by fluorescence in situ hybridization placed all these clones in band q11 of porcine Chr 6 (SSC6q11). Sequence analysis of the cosmids resulted in the characterization of an open reading frame (ORF), 1098 bp in length, that is 82.3% identical to the human FUT1 sequence; a second ORF, 1023 bp in length, 85% identical to the human FUT2 sequence; and a third FUT-like sequence thought to be a pseudogene. The FUT1 and FUT2 loci therefore seem to be the porcine equivalents of the human blood group H and Secretor loci. Direct sequencing of the two ORFs in swine being either susceptible or resistant to adhesion and colonization by F18 fimbriated Escherichia coli (ECF18) revealed two polymorphisms at bp 307 (M307) and bp 857 (M857) of the FUT1 ORF. Analysis of these mutations in 34 Swiss Landrace families with 221 progeny showed close linkage with the locus controlling resistance and susceptibility to E. coli F18 adhesion and colonization in the small intestine (ECF18R), and with the locus of the blood group inhibitor S. A high linkage disequilibrium of M307-ECF18R in Large White pigs makes the M307 mutation a good marker for marker-assisted selection of E. coli F18 adhesion-resistant animals in this breed. Whether the FUT1 or possibly the FUT2 gene products are involved in the synthesis of carbohydrate structures responsible for bacterial adhesion remains to be determined.

Adhesins, Escherichia coli↗

Breast cancer: zones of increased density mammographic features, correlated to clinical TNM and prognosis.

From January 1981 to December 1995, 8,421 patients having a mammographic opacity corresponding to breast cancer were examined. The opacities were divided into two groups: zones of increased density (ZID), (1,449 patients), and a reference group comprising all other types of opacities (6,972 patients). Mammograms were reviewed retrospectively, as well as clinical, histological and biological parameters in both groups. Diagnosis of ZID was often difficult, sometime's guided by the presence of microcalcifications, which were more frequent. Sonography and direct mammographic magnification proved to be particularly helpful for a correct diagnosis. Most prognostic factors were poorer in ZID as compared to the reference group. The 5 year survival rate was 78% (84% for the reference group). Breast cancer that appears on mammograms as a ZID is often more difficult to diagnose and factors of poor prognosis are more often observed than in breast cancer with other types of opacities. To improve their detection sonography and direct mammographic magnification can be very helpful.

Breast Neoplasms↗

High-dose chemotherapy with carboplatin, etoposide and cyclophosphamide followed by a haematopoietic stem cell rescue in patients with high-risk retinoblastoma: a SFOP and SFGM study.

This study investigates the role of high-dose chemotherapy with haematopoietic stem cell rescue as consolidation treatment in high-risk retinoblastoma (extraocular disease at diagnosis or relapse or invasion of cut end of optic nerve). 25 patients received high-dose chemotherapy including carboplatin (250 mg/m2/day from day 1 to day 5 for the 6 first patients and 350 mg/m2/day from day 1 to day 5 for the other patients), etoposide (350 mg/m2/day from day 1 to day 5) and cyclophosphamide (1.6 g/m2/day from day 2 to day 5) (CARBOPEC) followed by autologous haematopoietic stem cell rescue. 19 patients received this drug combination for chemosensitive extraocular relapse. The other 6 patients with histological high-risk factors were given this treatment as consolidation after enucleation and conventional chemotherapy. The three year disease-free survival was 67.1%. In 7 of the 9 relapsing patients, the first site of relapse was the central nervous system. All patients with central nervous system disease died except one. The main toxicity was haematological and digestive (mucositis and diarrhoea). 2 of the 13 evaluable patients had grade III and IV ototoxicity. One patient experienced an acute grade I reversible cardiotoxicity. The CARBOPEC regimen seems to be a promising therapeutic strategy in patients with high-risk retinoblastoma, especially those with bone and/or bone marrow involvement. This treatment did not improve the outcome of patients with central nervous system disease.

Antineoplastic Combined Chemotherapy Protocols↗

Insulin-mediated secretion of ecdysteroids from mosquito ovaries and molecular cloning of the insulin receptor homologue from ovaries of bloodfed Aedes aegypti.

The reproductive cycle of female mosquitoes is activated by ingestion of blood from vertebrate hosts. Shortly after feeding, neurohormones are released from the brain neurosecretory system and stimulate the ovaries to secrete ecdysteroids, which are necessary for vitellogenesis by the fat body. Because bombyxins, which are insulin-like peptides, stimulate ecdysteriodgenesis in silkworm larvae, we tested porcine insulin and found that it activates ecdysteroidogenesis and protein synthesis in ovaries isolated from unfed mosquitoes. To further characterize the regulation of ecdysteroidogenesis in female mosquitoes, we cloned the mosquito insulin receptor (MIR) homologue from ovarian mRNA. The sequence of the extracellular domain shows moderate homologies with vertebrate and Drosophila insulin receptor homologues, as well as with the insulin receptor-related receptor, the latter being an "orphan" receptor with an unknown function. In the intracellular domain, high homologies are observed, particularly in those subdomains that are responsible for ATP binding and kinase activity. Northern blot analysis of MIR demonstrated a highly specific expression in ovaries, and cloning experiments indicated its presence in the brain. Recombinant MIR extracts from a baculovirus expression system contained high constitutive kinase activity in the presence of manganese or magnesium. Activation was independent of a ligand. SDS-gel analysis suggested that the recombinant receptor was not post-translationally processed into an alpha- and beta-subunit as was expected from a putative cleavage signal. Enzymatic properties of the proreceptor are presented: the Km for ATP was between 15 and 50 microM in the presence of a synthetic substrate: maximal kinase activity to 100-fold over basic activity was reached in the presence of 1 mM manganese. Stimulation of key oogenic processes by porcine insulin and identification of a MIR indicate that insulin-like neurohormones may have an important regulatory role in mosquito oogenesis.

Aedes↗

[Diagnosis of infraclinical lesions of the breast with dynamic MRI: results of a prospective and multicenter study].

AIM: To determine the accuracy of dynamic contrast-enhanced subfraction MRI to diagnose nonpalpable breast lesions in a prospective multicenter study. MATERIAL AND METHODS: From June to November 1994, 72 patients had a surgical biopsy for a nonpalpable breast lesion and a preoperative dynamic MR after an informed consent was obtained. MR examinations were performed on 0.5, 1 and 1.5T MR unit. Each center underwent dynamic sequences either in spin or gradient echo in T1 weighted images obtained in less than two minutes before and after injection of Gadolinium-DOTA. The presence/absence of contrast enhancement within two minutes after injection of Gadolinium were considered as positive/negative findings respectively. RESULTS: These 72 women had mammographic (n = 80) or ultrasonographic lesions (n = 2). Mammograms showed mass (n = 23), asymmetrical density (n = 2), architectural distorsion (n = 8), clustered microcalcifications (n = 47) or was normal (n = 2). Dynamic Breast MR imaging showed early contrast enhancement in 44 malignant lesions (sensitivity: 89.8%) and 13 benign lesions (specificity: 60.6%). Five intraductal carcinoma of comedo (n = 1) or non-comedo (n = 4) type did not demonstrate any early contrast enhancement. CONCLUSION: This prospective mulcentric study confirms the high sensitivity of dynamic breast MRI whatever the type of MR unit or sequences.

Adult↗

[A molecular test for the detection of E. coli F18 receptors: a breakthrough in the struggle against edema disease and post-weaning diarrhea in swine].

Oedema disease and post-weaning diarrhoea in swine are associated with the colonization of the intestine with toxigenic Escherichia (E.) coli bacteria of various serotypes. Colonization depends on specific binding between adhesive fimbriae and receptors on the enterocytes. The demonstration of these receptors allows the identification of susceptible and resistant pigs. Direct sequencing of the alpha (1,2) fucosyltransferase gene (FUT1) in swine being either susceptible or resistant to adhesion by F18 fimbriated E.coli revealed a mutation at basepair 307 (M307). Analysis of the mutation in Swiss Landrace and Large White families showed close linkage with the locus controlling resistance and susceptibility to E.coli F18 adhesion (ECF18R). The FUT1 (M307) mutation is a good marker for selection of E.coli of F18 adhesion resistant animals. The mutation is found with variable frequencies in Duroc, Hampshire and Pietrain pigs as well.

Animals↗

Involution of the lactating mammary gland is inhibited by the IGF system in a transgenic mouse model.

Development of the mammary gland during puberty, pregnancy, and lactation is controlled by steroid and peptide hormones and growth factors. To determine the role of the insulin-like growth factors (IGFs) in this process we developed a transgenic model using the whey acidic protein (WAP) gene to direct expression of rat IGF-I and human IGF binding protein-3 (IGFBP-3) to mammary tissue during late pregnancy and throughout lactation. High levels of expression of transgenic IGF-I and IGFBP-3 were seen in lobular-alveolar cells by in situ hybridization. There was no obvious effect on mammary development during pregnancy and lactation; indeed, mothers were capable of nursing their pups normally and the only structural difference seen in the mammary glands at peak lactation was an overall smaller size of the alveoli. We also evaluated the role of IGF-I and IGFBP-3 in the remodeling of mammary tissue during involution. Compared with control animals, the process of involution was modified in both transgenic lines. The degree of apoptotic cells was lower in the WAP-IGF-I and WAP-BP-3 expressing mice. In addition, there was a more quiescent pattern of involution with residual lobular secretary ability and a muted host inflammatory reaction with fewer lumenal microcalcifications. These results demonstrate that IGF-I and IGFBP-3 may modulate the involutionary process of the lactating mammary gland.

Animals↗

Long-range synchronization of oscillatory light responses in the cat retina and lateral geniculate nucleus.

Visual responses in the retina and the lateral geniculate nucleus (LGN) exhibit oscillatory patterning within a broad range of frequencies. Oscillatory activity is often associated with the synchronization of spatially distributed responses. Here we demonstrate, with simultaneous multi-electrode recordings from the retina and the LGN, that stationary and moving light stimuli evoke in retinal ganglion cells oscillatory responses in the frequency range of 61 to 114 Hz that become synchronized over distances larger than 20 degrees of visual angle across the nasal and temporal halves of the retina. This temporal patterning of retinal responses is transmitted reliably by LGN neurons, such that stimuli crossing the vertical meridian evoke synchronous responses in the LGNs of both hemispheres. The oscillatory responses are not phase-locked to the stimulus onset, indicating that synchronization results from horizontal interactions in the retina. The occurrence of synchronization depends on global stimulus properties such as size and continuity, suggesting that temporal correlation among responses of spatially segregated ganglion cells can be exploited to convey information relevant for perceptual grouping.

Animals↗

Could somatostatin scintigraphy be superior to MIBG scan in the staging of stage IVs neuroblastoma (Pepper's syndrome)?

A 4-month-old infant suffering from Stage IVs neuroblastoma (NB IVs; Pepper's syndrome) was repeatedly examined by I-123 MIBG and somatostatin analog in-111 pentetreotide (SMS) scintigraphy, during a 2-year period. Treatment was restricted to surgery of the primary tumor. I-123 MIBG and SMS scan results were positive in the primary tumor and liver, but I-123 MIBG yielded very poor images and failed to reliably detect bone marrow metastases in the lower limbs and skull, whereas SMS precisely visualized these lesions. Six months after diagnosis, the infant was in complete clinical remission. I-123 MIBG and SMS images had returned to normal at 1 year. The prognostic implication of positive SMS imaging, in combination with positive or negative I-123 MIBG scan results, is not known in NB IVs and requires further investigation.

3-Iodobenzylguanidine↗

Partial characterization of porcine obesity gene (OBS) and its localization to chromosome 18 by somatic cell hybrids.

Degenerate primers based on human and mouse obesity gene (OBS) sequencing data were used in the reverse transcriptase-polymerase chain reaction (RT-PCR) of total RNA from pig white adipose tissue. Both strands of the resultant pig- specific 325 bp DNA fragment were sequenced. Comparison of the obtained sequence with known sequences revealed an 86% identity with the human and 84% identity with the mouse OBS cDNA. The OBS gene was physically mapped to pig chromosome 18 by PCR analysis of somatic cell hybrids, using pig-specific primers. This result is consistent with the recent assignment of the human OBS gene to chromosome 7 and the observation made by comparative mapping that by using a human chromosome 7 specific library two segments of conserved synteny were detected on porcine chromosomes 9 and 18. We conclude the border of conserved synteny to be in the 7q31-7q32 region of the human chromosome.

Adipose Tissue↗

[Sedation with oral hydroxyzine and rectal chloral hydrate in pediatric MRI and CT].

AIM: To assess the efficacy and risks of oral hydroxyzine and rectal chloral hydrate to sedate children undergoing CT or MRI. PATIENTS AND METHODS: 110 children underwent 117 studies. Medical history, treatments, doses per kg of sedative drugs, study quality, sedation time and side effects were prospectively recorded. RESULTS: 25 minutes was the mean time necessary to put children to sleep, 59 minutes was the mean time of sedation 96% of studies were interpretable. 2 children showed transient side effects. CONCLUSION: This sedation regimen appeared efficient. However, its limitations and risks have to be known by radiologists. Sedation-related problems also have to be considered by hospital managers when a new CT or MR equipment is being acquired.

Administration, Oral↗

Insulin-like growth factor-I and insulin-like growth factor binding protein-3 inhibit involution of the mammary gland following lactation: studies in transgenic mice.

The role of the insulin-like growth factor system on mammary gland development and involution following pregnancy and lactation was studied. Transgenic mice expressing rat IGF-I and human IGFBP-3 specifically in the mammary gland tissue, were created using the whey acidic protein gene. Mammary gland development was normal in transgenic animals expressing either rIGF-I or hIGFBP-3. In contrast, involution of the gland was delayed in both groups of transgenic mice. Specifically, the number of apoptotic cells was less in the involuting glands of transgenic mice compared with control animals. These results confirm the hypothesis that the IGF system regulates mammary gland function.

Animals↗

Ductal carcinoma in situ: MR imaging-histopathologic correlation.

PURPOSE: To correlate histopathologic and magnetic resonance (MR) imaging findings of ductal carcinoma in situ (DCIS). MATERIALS AND METHODS: Thirty-six women with DCIS underwent preoperative contrast material-enhanced subtraction dynamic MR imaging. Concomitant early contrast enhancement in the breast parenchyma with normal vessels was considered a positive finding. The size and shape of early enhancement were correlated with the size and density packing of ducts involved by DCIS. Tumor angiogenesis in the stroma that surrounded the ducts was evaluated with immunoperoxidase staining. RESULTS: Early contrast enhancement was demonstrated in 34 patients with DCIS but not in two patients with comedo-type DCIS. Tumor angiogenesis was demonstrated in the stroma. The size and morphology of contrast-enhanced lesions significantly correlated with the size (P = .0085) and density packing of ducts involved by DCIS (P = .012). CONCLUSION: Contrast enhancement on dynamic MR images of DCIS may be due to the presence of tumor angiogenesis in the stroma.

Breast↗