PubMed Health⌕ Search

Biomedical subjects

L Bergman

Publications and source records attributed to L Bergman.

At least 19 recordsLinked to original sources
PubMed2005

A report of a national mutation testing service for the MEN1 gene: clinical presentations and implications for mutation testing.

INTRODUCTION: Mutation testing for the MEN1 gene is a useful method to diagnose and predict individuals who either have or will develop multiple endocrine neoplasia type 1 (MEN 1). Clinical selection criteria to identify patients who should be tested are needed, as mutation analysis is costly and time consuming. This study is a report of an Australian national mutation testing service for the MEN1 gene from referred patients with classical MEN 1 and various MEN 1-like conditions. RESULTS: All 55 MEN1 mutation positive patients had a family history of hyperparathyroidism, had hyperparathyroidism with one other MEN1 related tumour, or had hyperparathyroidism with multiglandular hyperplasia at a young age. We found 42 separate mutations and six recurring mutations from unrelated families, and evidence for a founder effect in five families with the same mutation. DISCUSSION: Our results indicate that mutations in genes other than MEN1 may cause familial isolated hyperparathyroidism and familial isolated pituitary tumours. CONCLUSIONS: We therefore suggest that routine germline MEN1 mutation testing of all cases of "classical" MEN1, familial hyperparathyroidism, and sporadic hyperparathyroidism with one other MEN1 related condition is justified by national testing services. We do not recommend routine sequencing of the promoter region between nucleotides 1234 and 1758 (Genbank accession no. U93237) as we could not detect any sequence variations within this region in any familial or sporadic cases of MEN1 related conditions lacking a MEN1 mutation. We also suggest that testing be considered for patients <30 years old with sporadic hyperparathyroidism and multigland hyperplasia.

Australia↗
PubMed2000

Risk and prognosis of endometrial cancer after tamoxifen for breast cancer. Comprehensive Cancer Centres' ALERT Group. Assessment of Liver and Endometrial cancer Risk following Tamoxifen.

BACKGROUND: Tamoxifen increases the risk of endometrial cancer. However, few studies have produced reliable risk estimates by duration, dose, and recency of use, or addressed the prognosis of endometrial cancers in tamoxifen-treated women. METHODS: We did a nationwide case-control study on the risk and prognosis of endometrial cancer after tamoxifen use for breast cancer. Information on tamoxifen use and other risk factors for endometrial cancer was obtained from 309 women with endometrial cancer after breast cancer (cases), and 860 matched controls with breast cancer but without endometrial cancer. For 276 cases, we obtained tissue blocks of endometrial cancer to review the diagnosis, and used immunohistochemistry to examine hormone-receptor status and overexpression of p53. FINDINGS: Tamoxifen had been used by 108 (36.1%) of 299 cases and 245 (28.5%) controls (relative risk 1.5 [95% CI 1.1-2.0]). Risk of endometrial cancer increased with longer duration of tamoxifen use (p < 0.001), with relative risks of 2.0 (1.2-3.2) for 2-5 years and 6.9 (2.4-19.4) for at least 5 years compared with non-users. Endometrial cancers of stage III and IV occurred more frequently in long-term tamoxifen users (> or = 2 years) than in non-users (17.4% vs 5.4%, p=0.006). Long-term users were more likely than non-users to have had malignant mixed mesodermal tumours or sarcomas of the endometrium (15.4% vs 2.9%, p < or = 0.02), p53-positive tumours (31.4% vs 18.2%, p=0.05), and negative oestrogen-receptor concentrations (60.8% vs 26.2%, p < or = 0.001). 3-year endometrial-cancer-specific survival was significantly worse for long-term tamoxifen users than for non-users (76% for > or = 5 years, 85% for 2-5 years vs 94% for non-users, p=0.02). INTERPRETATION: Long-term tamoxifen users have a worse prognosis of endometrial cancers, which seems to be due to less favourable histology and higher stage. However, the benefit of tamoxifen on breast-cancer survival far outweighs the increased mortality from endometrial cancer. Nevertheless, we seriously question widespread use of tamoxifen as a preventive agent against breast cancer in healthy women.

Aged↗
PubMed2000

Identification of MEN1 gene mutations in families with MEN 1 and related disorders.

Following identification of the MEN1 gene, we analysed patients from 12 MEN 1 families, 8 sporadic cases of MEN 1, and 13 patients with MEN 1-like symptoms (e.g. cases of familial isolated hyperparathyroidism (FIHPT), familial acromegaly, or atypical MEN 1 cases) for the presence of germline MEN1 mutations. The entire coding region of the MEN1 gene was sequenced, and mutations were detected in 11 MEN 1 families; one sporadic MEN 1 patient, one case of FIHPT and one MEN 1-like case. Constitutional DNA samples from individuals without MEN1 mutations were digested with several restriction enzymes, Southern blotted and probed with MEN1 cDNA to analyse for the presence of larger deletions of the MEN1 gene unable to be detected by PCR. One MEN 1 patient was found to carry such a deletion. This patient was heterozygous for the D418D polymorphism, however sequence analysis of RT-PCR products showed that only the variant allele was transcribed, thus confirming the result obtained by Southern analysis, which indicated loss of a region containing the initiation codon of one allele.

Acromegaly↗
PubMed2000

Identification of somatic mutations of the MEN1 gene in sporadic endocrine tumours.

Endocrine tumours of the pancreas, anterior pituitary or parathyroids arise either sporadically in the general population, or as a part of inherited syndromes such as multiple endocrine neoplasia type 1 (MEN 1). The mechanisms responsible for the development of sporadic endocrine lesions are not well understood, although loss of heterozygosity (LOH) of the MEN1 locus on chromosome 11q13 and somatic mutation of the MEN1 gene have been frequently associated with the development of MEN 1-type sporadic endocrine lesions. To further investigate the role of the MEN1 gene in sporadic endocrine tumorigenesis, we analysed DNA from 14 primary parathyroid lesions, 8 anterior pituitary tumours and 3 pancreatic tumours for the presence of somatic MEN1 gene mutations and LOH of seven microsatellite markers flanking the MEN1 locus. In addition, we similarly analysed 8 secondary parathyroid lesions which arose in patients with chronic renal failure. None of the patients studied had a family history of MEN 1. Three primary parathyroid lesions and one pancreatic tumour (glucagonoma) were found to have lost one allele at the MEN1 locus. Somatic mutations were identified by SSCP and sequence analysis in one of these parathyroid lesions (P320L) and in the glucagonoma (E179V). These results support previous findings that inactivation of the MEN1 tumour suppressor gene contributes to the development of sporadic MEN 1-type endocrine lesions but is not associated with the development of parathyroid hyperplasia seen in some renal failure patients.

Adenoma↗
PubMed1999

A 500-kb sequence-ready cosmid contig and transcript map of the MEN1 region on 11q13.

We have generated a transcript map of an approximately 1.2-Mb region from human chromosome band 11q13 between the loci VEGFB and CAPN1, which flank the multiple endocrine neoplasia type 1 (MEN 1) locus. In total, we isolated 144 cosmids from this region and generated a sequence-ready cosmid contig of the approximately 500-kb region between the neurexin locus and D11S2196E. We identified 54 genes/ESTs by sample sequencing and have constructed a transcript map of this region. Genes were found to be clustered in three regions, and one of these genes was identical to the recently identified MEN1 locus. Relative to the latter, we have mapped the positions of 13 known genes, 18 genes which show homology to genes from humans or other organisms, and 22 genes/ESTs that appear novel. In addition, we have ascertained the directions of transcription of some of these genes and have determined intergenic distances between many loci. Full characterization of some of these genes, as well as the novel ESTs, will be useful in identifying candidate genes for other diseases known to map to this chromosomal region.

Animals↗
PubMed1998

Characterization of the mouse Men1 gene and its expression during development.

The gene responsible for multiple endocrine neoplasia type 1 (MEN1), a heritable predisposition to endocrine tumours in man, has recently been identified. Here we have characterized the murine homologue with regard to cDNA sequence, genomic structure, expression pattern and chromosomal localisation. The murine Men1 gene spans approximately 6.7 kb of genomic DNA and is comprised of 10 exons with similar genomic structure to the human locus. It was mapped to the pericentromeric region of mouse chromosome 19, which is conserved with the human 11q13 band where MEN1 is located. The predicted protein is 611 amino acids in length and overall is 97% homologous to the human orthologue. The 45 reported MEN1 mutations which alter or delete a single amino acid in human all occur at conserved residues, thereby supporting their functional significance. Two transcripts of approximately 3.2 and 2.8 kb were detected in both embryonal and adult murine tissues, resulting from alternative splicing of intron 1. By RNA in situ hybridization and Northern analysis the spatiotemporal expression pattern of Men1 was determined during mouse development. Men1 gene activity was detected already at gestational day 7. At embryonic day 14 expression was generally high throughout the embryo, while at day 17 the thymus, skeletal muscle, and CNS showed the strongest signal. In selected tissues from postnatal mouse Men1 was detected in all tissues analysed and was expressed at high levels in cerebral cortex, hippocampus, testis, and thymus. In brain the menin protein was detected mainly in nerve cell nuclei, whereas in testis it appeared perinuclear in spermatogonia. These results show that Men1 expression is not confined to organs affected in MEN1, suggesting that Men1 has a significant function in many different cell types including the CNS and testis.

Amino Acid Sequence↗
PubMed1998

Mutation analysis of the MEN1 gene in multiple endocrine neoplasia type 1, familial acromegaly and familial isolated hyperparathyroidism.

Multiple endocrine neoplasia type 1 (MEN 1) is an autosomal dominant disease characterized by neoplasia of the parathyroid glands, the endocrine pancreas, and the anterior pituitary gland. In addition, families with isolated endocrine neoplasia, notably familial isolated hyperparathyroidism (FIHP) and familial acromegaly, have also been reported. However, whether these families constitute MEN 1 variants or separate entities remains speculative as the genetic bases for these diseases are unclear. The gene for MEN 1 has recently been cloned and characterized. Using single strand conformation analysis (SSCA) and sequencing, we performed mutation analysis in: a) a total of 55 MEN 1 families from 7 countries, b) 13 isolated MEN 1 cases without family history of the disease, c) 8 acromegaly families, and d) 4 FIHP families. Mutations were identified in 27 MEN 1 families and 9 isolated cases. The 22 different mutations spread across most of the 9 translated exons and included frameshift (11), nonsense (6), splice (2), missense mutations (2), and in-frame deletions (1). Among the 19 Finnish MEN 1 probands, a 1466del12 mutation was identified in 6 families with identical 11q13 haplotypes and in 2 isolated cases indicating a common founder. One frameshift mutation caused by 359del4 (GTCT) was found in 1 isolated case and 4 kindreds of different origin and haplotypes; this mutation therefore represents a common "warm" spot in the MEN1 gene. By analyzing the DNA of the parents of an isolated case one mutation was confirmed to be de novo. No mutation was found in any of the acromegaly and small FIHP families, suggesting that genetic defects other than the MEN1 gene might be involved and that additional such families need to be analyzed.

Acromegaly↗
PubMed1997

Analysis of loss of heterozygosity and KRAS2 mutations in ovarian neoplasms: clinicopathological correlations.

The molecular events that give rise to ovarian epithelial neoplasms are not well understood. In particular, it is not known whether adenocarcinomas arise from benign or low malignant potential (LMP) precursors. We have examined a large series of benign (25) and LMP (31) ovarian tumors for loss of heterozygosity (LOH) at multiple loci on 17 chromosomes. LOH was observed in benign tumors on chromosomes 6 (14%) and 9 (5%) and on the X chromosome (33%) only. LOH on these chromosomes was also detected in a small number of LMP neoplasms, suggesting that these may derive sometimes from benign precursors. In addition, we examined LOH in 93 adenocarcinomas. Analysis of associations between LOH events showed that LOH on chromosomes 5 and 17 (P = 0.0002) and on chromosomes 17 and 18 (P = 0.00007) were associated significantly with each other, which suggests that these may represent cooperative, progressive events. No novel significant associations were identified between LOH events and stage, grade, or histology, which would indicate the existence of genetic heterogeneity in ovarian neoplasms. KRAS2 mutations were detected more often in LMP neoplasms than in malignant tumors (P = 0.004) and were detected more often in Stage I/II malignant tumors than in Stage III/IV malignant tumors (P = 0.033), suggesting that LMP tumors with KRAS2 mutations are unlikely to progress to frank malignancy. Univariate (but not multivariate) survival analysis showed that LOH of chromosomes 11 (P = 0.039) and 17 (P = 0.04) was associated with a significantly worse prognosis. Replication of these novel findings is necessary, and the identification, isolation, and characterization of the critical genes affected by LOH will determine their importance in the pathogenesis of ovarian malignancies.

Chromosome Deletion↗
PubMed1996

Marked symptom reduction in two women with bulimia nervosa treated with the testosterone receptor antagonist flutamide.

Previous reports indicate that elevated serum levels of androgens in women may contribute to the development of bulimia nervosa and other conditions characterized by impaired impulse control and/or depressed mood. This report describes the effect of treatment with the testosterone antagonist flutamide (250-500 mg daily) in two women with severe bulimia. Both subjects reported a marked improvement with respect to bulimic behaviour within a week after initiation of flutamide treatment; when the drug was withdrawn, both patients relapsed. It is concluded that further investigations of the possible efficacy of androgen antagonism in eating disorders are warranted.

Adult↗
PubMed1996

Limbal sub-Tenon's administration of retrobulbar anesthesia using a blunt irrigating cannula.

BACKGROUND AND OBJECTIVE: To eliminate sharp needles when administering local anesthesia to the eye in order to reduce serious complications caused by needle perforation. PATIENTS AND METHODS: After topical anesthesia, limbal conjunctival incision, and sub-Tenon's dissection, a retrobulbar irrigation of an equal mixture of bupivacaine (5 mg/ml) and lidocaine (20 mg/ml) was given using a blunt cannula. RESULTS: The technique was used in both vitreoretinal surgery (n = 70) and anterior segment surgery (n = 235) with good analgesic and akinetic effects. No serious adverse were noted. CONCLUSION: This proved to be a safe and efficient technique that abandoned the use of sharp needles.

Adult↗
PubMed1995

Should tamoxifen be a primary treatment choice for elderly breast cancer patients with locoregional disease?

UNLABELLED: To determine the efficacy of tamoxifen as primary treatment for elderly breast cancer patients with locoregional disease, the medical records of 85 patients of 75 years and older were reviewed. The median follow-up was 28 months (range 3-97 mo). Complete remission occurred in twelve (14.1%) patients. All of these patients remained in remission until death or closing date of the study. Twenty (23.5%) patients responded with a partial remission; 5 of them subsequently developed tumor progression. Thirteen (15.3%) patients developed initial tumor progression and 39 (45.9%) had disease stabilisation. Nineteen of this latter group subsequently developed tumor progression. Out of 37 (43.5%) patients with tumor progression, 14 patients were salvaged by surgery (n = 13) or radiotherapy (n = 1). Until the closing date of the study, disease could not be controlled by secondary treatment in 12 patients who subsequently died of breast cancer. Twenty-two of the 37 patients were unfit for surgical treatment at progression, of whom 14 were operable at diagnosis. The actuarial 5-year observed survival rate was 40% for the whole patient group. CONCLUSIONS: Although some patients (14.1%) managed to maintain a long lasting complete remission, caution should be preserved in using tamoxifen as first-line treatment, because of the high risk of treatment failures. As long as factors can not be identified to predict which subgroups of patients will respond to tamoxifen with a remission lasting for their life-time, tamoxifen may only provide an acceptable alternative for elderly breast cancer patients who are too frail or are unwilling to undergo surgery or radiotherapy. For elderly patients in good physical condition, primary treatment by (ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1995

Meropenem versus imipenem/cilastatin in the treatment of intra-abdominal infections.

In order to compare the clinical and microbiological efficacy and safety of meropenem with imipenem/cilastatin, 249 patients with intra-abdominal infections participated in an open randomised comparative multicentre trial. Seventy-five men and 57 women (mean age 51 years) were enrolled in the meropenem group and 67 men and 50 women (mean age 52 years) in the imipenem/cilastatin group. The patients received either meropenem, 500 mg q 8 h, or imipenem/cilastatin, 500 mg/500 mg q 8 h by intravenous infusion for up to 17 days (mean 5 days). Ninety-seven of 99 patients (98%) receiving meropenem were clinically cured while 86 of 90 patients (96%) in the imipenem/cilastatin group were clinically cured. The microbiological response was satisfactory in 89 of 94 evaluable patients (95%) receiving meropenem and in 78 of 81 evaluable patients (96%) receiving imipenem/cilastatin. There was no significant difference in clinical and microbiological efficacy between the two treatment groups. Adverse reactions were noted in 26 patients receiving meropenem and in 36 patients receiving imipenem/cilastatin. The present study shows that meropenem is effective and well tolerated in the treatment of intra-abdominal infections.

APACHE↗
PubMed1995

Microscopic colitis syndrome.

The colorectal biopsy specimens from 30 patients with chronic watery diarrhoea but normal endoscopic and radiographic findings were studied by light microscopy, morphometry, immunohistochemistry, and two patients with electron microscopy. The histological changes in the colorectum were originally diagnosed in six patients as lymphocytic colitis and in 24 patients as collagenous colitis. The analysis of the specimens for this study could delineate three distinct groups of microscopic colitis: lymphocytic colitis (six patients), collagenous colitis without lymphocytic attack on the surface epithelium (seven patients), and a mixed form presenting with both thickening of the collagen plate and increased number of intraepithelial lymphocytes (17 patients). No transformation was seen from one type to another during follow up of six patients for four to seven years. Increased numbers of active pericryptal myofibroblasts were found with the electron microscope in one patient with mixed microscopic colitis showing also myofibroblasts entrapped within the collagen layer. Hitherto undescribed flat mucosa of the ileum was found in one patient with lymphocytic colitis and both flat mucosa and thickening of the collagen plate in the ileum were seen in one patient with the mixed form of the disease. In another patient with mixed microscopic colitis, normalisation of the colorectal morphology occurred after temporary loop ileostomy, followed by the reappearance of both diarrhoea, inflammation, and thickening of the collagen plate after the ileostomy was reversed. No association was found between non-steroid anti-inflammatory drug (NSAID) consumption and collagenous or mixed microscopic colitis. The primary cause of microscopic colitis is probably an immunological reaction to luminal antigen/s, perhaps of ileal origin. The engagement of the pericryptal myofibroblasts in the disease process might result in the development of the various forms of microscopic colitis. An inverse relation between intraepithelial lymphocyte count and collagen thickness may indicate that microscopic colitis is a spectral disease.

Adult↗
PubMed1995

Costs of medical care after first-ever stroke in The Netherlands.

BACKGROUND AND PURPOSE: Stroke causes high morbidity and mortality. The aging of the population further increases the demands on healthcare costs. METHODS: We estimated the lifetime direct costs of care of first-ever stroke patients in the Netherlands in 1991 using epidemiological data from national and international studies. In addition, we examined the effect of an aging population on future healthcare costs. RESULTS: The lifetime costs for 24,007 first-ever stroke patients are estimated to be 1870 million Dutch guilders (Dfl) (1 Dfl = 0.53 US dollar, 1991). Per-person costs are higher for women (83,000 Dfl) than for men (71,000 Dfl). The major cost component of first-year costs is hospital costs (45%), while nursing home costs dominate lifetime costs (50%). An increase of the elderly population older than 65 years of 27% between 1991 and 2010 might lead to a parallel increase of total costs of 30%, or 1.5% per year. CONCLUSIONS: Long-term care rather than acute care dominates the lifetime costs for stroke patients now and in the future.

Aged↗
PubMed1995

Olsalazine versus sulphasalazine for relapse prevention in ulcerative colitis: a multicenter study.

OBJECTIVE: To compare the relapse-preventing effect and the frequency of adverse events of olsalazine and sulphasalazine in sulphasalazine-tolerant patients with ulcerative colitis. METHODS: Patients in remission, with at least two episodes of active disease during the last 5 yr, were randomized to 2 g of sulphasalazine or 1 g of olsalazine daily and were followed for 6-18 months. Relapse rates in the two groups were compared using frequency and life-table analysis. Sixty-nine patients with proctitis, 140 with left-sided colitis, and 113 with subtotal or total colitis were evaluated. RESULTS: In the intention-to-treat analysis, the failure rate (relapses plus withdrawals) was 54.7% in the olsalazine and 47.2% in the sulphasalazine group. In the per-protocol analysis excluding withdrawals, 44.7% relapsed in the olsalazine and 39.3% in the sulphasalazine group. Remission curves did not differ significantly, although at all time intervals the frequency of remission was slightly higher in the sulphasalazine group (p = 0.19 in the intention-to-treat analysis and p = 0.42 in the per-protocol analysis estimated by the log-rank test). Twelve patients (of whom five had diarrhea) in the olsalazine group versus eight patients in the sulphasalazine group discontinued the study because of side effects. CONCLUSION: The relapse-preventing effect of olsalazine and sulphasalazine in sulphasalazine-tolerant patients did not differ. Furthermore, the tolerability of olsalazine, particularly concerning diarrhea, appears to be better than previously reported.

Adult↗
PubMed1994

High levels of free testosterone in women with bulimia nervosa.

Women with normal-weight bulimia nervosa (n = 11) displayed significantly higher serum levels of free testosterone than age-matched controls (6.0 +/- 0.7 vs 3.9 +/- 0.8 pmol/l; P = 0.03). The possible importance of androgens, in women, for the pathophysiology of conditions characterized by an impairment in impulse control is being discussed.

Adult↗
PubMed1992

The influence of age on treatment choice and survival of elderly breast cancer patients in south-eastern Netherlands: a population-based study.

The influence of age on treatment choice and survival was studied in 2268 breast cancer patients of 55 years and older reported to the Eindhoven Cancer Registry from 1975 to 1987. Among patients of 75 years and older, stage I and II tumours occurred less often, whereas stage IIIb and undefined tumours occurred more often than among younger patients. Physicians were found to be less likely to treat women of 75 years and older with adjuvant radiotherapy after a mastectomy. Instead, these women received either surgery alone or surgery followed by hormonal therapy. Surgical procedures in the oldest age group were also less extensive. The 10-year relative survival for women over 74 years (32%) was significantly worse than that for younger patients (57%). Multivariate analyses showed that this poor outcome for the oldest age group was largely related to their unfavourable stage distribution: stage-specific survival appeared to be similar in all age groups. Age-related differences in treatment did not have an effect on survival.

Age Factors↗