Development of an SNP-based parentage verification panel for lovebirds.

The genus Agapornis, or lovebirds, are popular pet parrots worldwide. Currently, breeders are dependent on pedigree records as a selection tool as no molecular parentage verification test is available for any of the nine species. The A. roseicollis reference genome was recently assembled. This was followed by the sequencing of the whole genomes of the parents of the reference genome individual at 30× coverage. The parents' reads were mapped against the reference genome to identify SNPs. Over 1.6 million SNPs, shared between the parents, were discovered using the Genome Analysis Toolkit pipeline. SNPs were filtered to a panel of 480 SNPs based on Genome Analysis Toolkit parameters. The panel of 480 SNPs was genotyped in a population of 960 lovebirds across seven species. A panel of 262 SNPs was compiled that included SNPs successfully amplified across all species. The 262-SNP panel was reduced based on the observed heterozygosity (HO ) and minor allele frequency (MAF) values per SNP to include the lowest number of SNPs with the highest exclusion power for parentage verification. Two smaller panels consisting of 195 SNPs with MAF and HO values >0.1 and 40 SNPs with MAF and HO values >0.3, were constructed. The panels were verified using 43 families from different species with known relationships to evaluate the exclusion power of each panel. The 195 SNP panel with an average exclusion probability of 99.9% and MAF and HO values >0.1 was proposed as the routine Agapornis parentage verification panel.

Periodic follow-up after breast cancer and the effect on survival.

OBJECTIVE: To assess the role of routine follow-up in current management of breast cancer. DESIGN: Retrospective review. SETTING: Teaching hospital, The Netherlands. SUBJECTS: 270 patients who presented with recurrent breast cancer, 1974-90. MAIN OUTCOME MEASURE: Recurrence was coded as asymptomatic or symptomatic and related to survival. RESULTS: 170 (63%) of the recurrences were detected when they were symptomatic and 100 (37%) when they were not. The groups differed significantly according to the site of recurrence; 45/100 recurrences were local in the asymptomatic group compared with 23/170 (14%) in the symptomatic group. There was no significant difference in disease-free survival between the two groups. Overall 5-year survival after primary treatment for all recurrences (locoregional and distant) was significantly better (p=0.0003) in the asymptomatic group (62/100) than in the symptomatic group 79/170 (46%). However, when locoregional and distant recurrences were analysed separately no significant differences were found between both groups in overall survival after primary treatment or survival after detection of recurrence. The 5-year overall survival after primary treatment for distant recurrence was 26/47 (55%) in the asymptomatic group compared with 62/134 (46%) in the symptomatic group (p=0.13). For locoregional recurrence these figures were 35/45 (78%) and 14/23 (61%), respectively (p=0.34). Routine follow-up hardly affected the course of locoregional recurrence. Only five of 75 patients with local recurrence (7%) developed uncontrolled local disease, 2 of whom were initially detected during routine follow-up. CONCLUSIONS: We conclude that in the current management of breast cancer the medical impact of follow-up is low, so follow-up visits after treatment for breast cancer are hardly warranted.

Synthesis and use of FSCPX, an irreversible adenosine A1 antagonist, as a 'receptor knock-down' tool.

A new preparative synthetic route for the irreversible adenosine A1 antagonist 8-cyclopentyl-3-N-[3-((3-(4-fluorosulphonyl)benzoyl)-oxy)-propyl]-1-N-propyl-xanthine (FSCPX, 1) is described. The availability of ample amounts of the irreversible antagonist FSCPX allowed us to use FSCPX as a research tool for adenosine A1 receptors in in vivo experiments. After verification of the irreversible antagonistic function of FSCPX in in vitro experiments, FSCPX was used successfully as a 'receptor knock-down' tool in in vivo experiments on conscious rats.

Screen-detected breast cancers have a lower mitotic activity index.

We know that screening for breast cancer leads to detection of smaller tumours with less lymph node metastases. Could it be possible that the decrease in mortality after screening is not only caused by this earlier stage, but also by a different mitotic activity index (MAI) of the tumours that are detected by screening? Is MAI a prognostic factor for recurrence-free survival? A retrospective study was carried out of 387 patients with breast cancer, treated at the University Hospital Nijmegen between January 1992 and September 1997. Ninety patients had screen-detected breast cancer, 297 patients had breast cancers detected outside the screening programme. The MAI, other prognostic factors and recurrence-free survival were determined. In non-screen-detected tumours the MAI is twice as high as in screen-detected tumours, even after correction for age took place. The MAI correlated well with other tumour characteristics. The MAI in itself is a prognostic factor for recurrence-free survival. Favourable outcome in screen detected breast cancer is not entirely caused by detecting cancer in early stages: quantitative features such as the MAI indicate a less malignant character of screen detected breast cancer. The MAI is an independent prognostic factor for recurrence-free survival.

Post-radiation lower motor neuron syndrome.

UNLABELLED: Objective To describe the clinical features of four patients we encountered with post-radiation lower motor neuron syndromes and to review the related literature BACKGROUND.: Radiation therapy for malignant neoplasms has been associated with a post-radiation lower motor neuron syndrome (PRLMNS). The earliest descriptions date back to World War II. METHODS: We evaluated four patients who developed a lower motor neuron syndrome several years after the completion of radiation therapy to treat malignancies. The clinical and electrophysiological features of these patients are described. RESULTS: Our patients with PRLMNS developed weakness, muscle atrophy, loss of reflexes, and fasciculations in myotomal distributions that corresponded to the regions that had been exposed to radiation The mean time between radiation exposure and onset of motor symptoms was 14 years. Sensory symptoms were either absent or minor. Motor and sensory nerve conduction studies were normal or only mildly affected, Needle electromyography showed varying degrees of active and chronic denervation changes, primarily in the distributions that had received radiation. Magnetic resonance imaging of the spine and myelography were unremarkable. Serum creatine kinase levels were elevated in two patients. The patients followed a stable to slowly progressive course at a mean follow up of 6.5 years. CONCLUSIONS: . Patients presenting with lower motor neuron syndromes should be questioned about prior radiation exposure. A diagnosis of PRLMNS carries a relatively favorable prognosis when compared with amyotrophic lateral sclerosis, another acquired motor neuron disorder.

Malignant fibrous histiocytoma of the stomach during pregnancy: a case report.

In this case report we describe a patient with a primary malignant fibrous histiocytoma of the stomach, diagnosed and operated upon during the sixth month of pregnancy. We stress the importance of a thorough diagnostic examination in cases of severe anaemia during pregnancy. Although very rare, malignancy of the gastrointestinal tract should be taken in consideration. No holding back is justified in diagnostic and therapeutic measurements because of pregnancy. Radiologic examination of the gastrointestinal tract should be replaced by endoscopy.

Infiltrating lobular carcinoma of the breast detected by screening.

BACKGROUND: This study was a retrospective analysis of all patients with invasive lobular breast cancer who presented to the University Hospital Nijmegen between 1980 and 1990, with follow-up to December 1992. A comparison was made between the invasive lobular carcinomas detected by breast cancer screening and those detected outside the screening project. METHODS: The total number of patients with breast cancer during this interval was 937, of whom 136 (14.5 per cent) had pure infiltrating lobular carcinoma (ILC). Breast cancer screening identified a total of 158 patients with infiltrating breast carcinoma of whom 20 (12.7 per cent) had ILC. Outside the screening programme a total of 116 patients with ILC were diagnosed during the same interval. RESULTS: The 2- and 5- and 10-year disease-free survival rate in the screen-detected group was 100, 100 and 89 per cent respectively. For the group outside the screening programme this was 88.4, 74.3 and 72.5 per cent respectively (P = 0.04). No patient in the screen-detected group died from breast cancer during follow-up, whereas the 2- and 5- and 10-year breast cancer survival rate for the group detected outside the screening programme was 96.5, 89.1 and 70.6 per cent respectively (P = 0.06). CONCLUSION: Between 10 and 15 per cent of patients with invasive lobular breast cancer can be detected by breast screening. These patients have a favourable outcome compared with those who have ILC detected outside the screening programme.

False-negative MR imaging of malignant breast tumors.

In this study we analyze MR-negative malignant lesions of the breast. A total of 204 patients with palpable and/or mammographic lesions were studied. The MR technique consisted of the turbo FLASH and MP-RAGE subtraction techniques. All patients underwent surgical biopsy and/or mastectomy and all specimens were examined by the correlative radiologic-histologic mapping technique. A total of 208 lesions were evaluated; 145 turned out to be malignant and 63 proved to be benign. Six malignant lesions were misinterpreted as benign on MR imaging; thus, suspicious contrast enhancement was present in 96 % of the lesions detected by mammography, US, or clinical examination. Especially 4 of the 17 ductal carcinoma in situ (DCIS) lesions were misinterpreted (23.5 %). Despite optimal technique, 6 malignant lesions were not identified by MR imaging. The highest prevalence of these MR occult lesions was in the group of DCIS. Although MR imaging has an important role in the evaluation of breast lesions and, primarily, in ruling out malignancy, one should be aware of the fact that false-negative MR findings do occur.

Interval carcinomas of the breast: a group with intermediate outcome.

BACKGROUND: Interval carcinoma is defined as a carcinoma detected between two mammographic screening rounds after a negative screening. By some authors these carcinomas are considered to be more aggressive than screen-detected carcinomas. METHODS: In a group of 937 patients referred for breast cancer in the period 1975-1990, 76 interval carcinoma patients were treated. In a retrospective study the outcome was studied of patients with an interval carcinoma in comparison with patients with screen-detected carcinomas and of patients with clinically detected carcinomas outside the screening program. RESULTS: No significant difference was found in the 5-year and 10-year disease-free survival of patients with interval carcinoma (80%, 68%) and the screen-detected group (89%, 81%) (P = 0.12). The interval group did significantly better than the patients with carcinomas detected outside the screening program (P = 0.03). CONCLUSION: Interval-detected cancers for patients in the screening program had an outcome intermediate between patients with screen-detected cancers and patients with cancers detected outside the screening program. The difference between interval-detected cancers and cancers detected outside the screening program was significant, whereas the difference between screen-detected and interval cancers was not.

MR characterization of suspicious breast lesions with a gadolinium-enhanced TurboFLASH subtraction technique.

PURPOSE: To assess the utility of gadolinium-enhanced dynamic magnetic resonance (MR) imaging with turbo fast low-angle shot (TurboFLASH) technique in the differentiation of benign from malignant lesions of the breast. MATERIALS AND METHODS: Contrast material-enhanced MR images were obtained at intervals of 2.3 seconds for 2 minutes. After the first four images were obtained, contrast medium was intravenously injected within 10 seconds. Lesions that enhanced within 11.5 seconds after the aorta opacified were regarded as malignant. Lesions that enhanced more than 11.5 seconds after the aorta were regarded as benign. A centrifugal pattern of enhancement was regarded as a sign that a lesion was benign. RESULTS: Eighty-seven lesions were evaluated. Histologic examination showed 65 lesions were malignant and 22 were benign. Gadolinium-enhanced TurboFLASH imaging had a sensitivity of 95%, a specificity of 86%, and an overall accuracy of 93% in differentiating benign from malignant lesions. CONCLUSION: Gadolinium-enhanced TurboFLASH imaging is a valuable method in the examination of breast lesions suspected of being malignant.

Role of gastroenterostomy in the palliative surgical treatment of pancreatic cancer.

The records of 72 consecutive patients with unresectable pancreatic cancer treated between 1974 and 1986 were evaluated to determine whether gastroenterostomy should be performed on a routine basis at initial intervention or on a therapeutic basis. Fourteen patients underwent an explorative laparotomy, 41 patients underwent biliary bypass, and 17 patients required biliary bypass and therapeutic gastroenterostomy at initial laparotomy. The mortality and morbidity rates in this last group were 18 and 59%, respectively. The most common complication was delayed gastric emptying (29%). Of the 37% of patients who required gastroenterostomy after initial biliary bypass, the mortality rate was 50% and delayed gastric emptying occurred in 57%. The mean survival after biliary bypass was 9.4 months while survival after therapeutic gastroenterostomy averaged 4.2 months. These findings suggest that gastroenterostomy should be performed on a prophylactic basis at initial intervention, unless a limited survival is expected.

[Extra-long plate osteosynthesis in femoral fractures]. / Extralange Plattenosteosynthese bei Femurfrakturen.

Of 252 femoral shaft fractures seen within a 9-year period, 32 (13%) were treated by internal fixation with an extra long DC plate, mainly because of severe comminution or fractures at two or more levels. Depending on the localization of the fracture, extra long, straight or angled plates were used. Half of the 32 patients showed multiple other injuries (mean ISS 39). Delayed union was seen in 4 patients, necessitating repeat osteosynthesis in 2. Postoperative osteitis was seen in 1 patient. The average time for consolidation was 22 weeks (10-50 weeks). The mean duration of hospitalization was 31 days. Apart from specific complications resulting from other severe injuries in 2 patients, the overall functional results were good.

Residual tumour after biopsy for non-palpable ductal carcinoma in situ of the breast.

In a group of 40 patients with non-palpable ductal carcinoma in situ (DCIS) of the breast, 41 breast specimens were available for studying residual tumour after biopsy. In one group of ten patients seen before 1977, simple histological examination revealed a 9 per cent incidence of residual tumour. However, after thorough examination residual foci of DCIS were found in 77 per cent of a subsequent group of 30 patients. This means that the majority of patients would have had to undergo reoperation if a breast-saving procedure had been performed. This fact must be taken into account when planning treatment of patients with non-palpable DCIS.

Treatment and survival of female patients with nonpalpable breast carcinoma.

Since 1971, 151 nonpalpable breast cancers (100 invasive carcinomas, 39 in situ ductal carcinomas, and twelve lobular carcinomas in situ) have been diagnosed and treated at the St. Radboud University Hospital. Of the 100 clinically occult invasive carcinomas, 53 had pathologic diameters of more than 10 mm, 29 were of sizes between 6 and 10 mm, and 18 were tumors of 5 mm or less. Residual tumor outside the "excisional" biopsy cavity was encountered in 76 of the 118 mastectomy specimens (64.4%) fully capable of evaluation. Invasive residual tumor would have been left behind in 34 of 86 mastectomy specimens (39.5%). Of 27 axillas studied, no patient with in situ carcinoma had evidence of axillary lymph node metastases. Invasive carcinoma, however, showed axillary lymph node involvement in 7.7% of mastectomy specimens when the size of the primary tumor was not more than 5 mm, in 12.5% when the size was between 6 and 10 mm, and in 29.5% when the primary tumor was more than 10 mm in diameter. The 10-year recurrence-free survival (RFS) of patients with clinically occult invasive carcinomas greater than 10 mm in size was 71.9% and differed significantly from the 90.9% for patients with the invasive tumors less than or equal to 5 mm, as well as from the 100% RFS of patients with invasive tumors of between 6 and 10 mm and noninvasive tumors. Although the 10-year RFS was 92.6% for the patients with negative axillary nodes and 80.0% for the patients with positive axillary nodes, this difference did not reach statistical significance. However, the disease-specific overall survival after 10 years was significantly different between node-negative patients (96.4%) and node-positive patients (78.8%). Multivariate analysis disclosed that the relationship between size of the primary tumor and RFS was independent of the presence of axillary lymph node metastases. In conclusion, the validity of the concept of minimal breast cancer has been re-enforced. However, the results of this study suggest that the upper limit of the original definition of minimal breast cancer is too narrow and should be extended, so that, apart from the noninvasive tumors--regardless of their size--all invasive tumors having a maximum diameter less than or equal to 10 mm should be regarded as minimal breast cancers.