There is no association between combined oral hormonal contraceptives and depression: a Swedish register-based cohort study.

OBJECTIVE: To investigate whether users of hormonal contraceptives (HCs) are at increased risk of depression compared with non-users. DESIGN: Register-based cohort study. SETTING: Sweden. SAMPLE: Women aged 15-25 years between 2010 and 2017 with no prior antidepressant treatment, psychiatric diagnose or contraindication for HCs (n = 739 585). METHODS: Women with a prescription of HC were identified via the Swedish Prescribed Drug Register (SPDR). Relative risks (RRs) for first depression diagnosis in current HC-users compared with non-users were modelled by Poisson regression. Adjustments included age, medical indication for HC-use and parental history of mental disorders, among others. MAIN OUTCOME MEASURES: Depression, captured by a redeemed prescription of antidepressant treatment, or a first depression diagnosis in the SPDR and the National Patient Register. RESULTS: Compared with non-users, women on combined oral contraceptives (COCs) and oral progestogen-only products had lower or no increased risk of depression, relative risk (RR) 0.89 (95% CI 0.87-0.91) and 1.03 (95% CI 0.99-1.06) after adjustments, respectively. Age-stratified analyses demonstrated that COC use in adolescents conferred no increase in risk (RR 0.96, 95% CI 0.93-0.98), whereas use of progestogen-only pills (RR 1.13, 95% CI 1.07-1.19), contraceptive patch/vaginal ring (RR 1.43, 95% CI 1.30-1.58), implant (RR 1.38, 95% CI 1.30-1.45) or a levonorgestrel intrauterine device (RR 1.59, 95% CI 1.46-1.73) were associated with increased risks. CONCLUSIONS: This study did not find any association between use of COCs, which is the dominating HC in first time users, and depression. Non-oral products were associated with increased risks. Residual confounding must be addressed in the interpretation of the results. TWEETABLE ABSTRACT: There is no association between combined hormonal contraceptives and depression.

Idiopathic ventricular fibrillation - Long term prognosis in relation to clinical findings and ECG patterns in a Swedish cohort.

BACKGROUND: Idiopathic ventricular fibrillation (IVF) is a rare cause of sudden cardiac arrest which may pose therapeutic and prognostic challenges. To date, the only effective treatment for survivors of cardiac arrest is the insertion of an implantable cardioverter-defibrillator (ICD). We sought to review the long-term outcome of a Swedish cohort with IVF. METHODS AND RESULTS: Fifty patients with IVF diagnosis between 1988 and 2016 (mean age at index 34.3, 56% male), were followed for a median 13.8 years in this retrospective multicenter observational study. No cardiac mortality was reported. 32% (n = 16) of patients had recurrence of ventricular fibrillation or sustained ventricular tachycardia, requiring ICD therapy, at a median time of 1.9 years (range 0.1-20.3) from the index event. Annual incidence rate of ventricular tachyarrhythmia was 3.1%. Abnormal ECG at baseline did not predict appropriate ICD therapy (p = 0.56). During the follow-up period, 14% (n = 7) patients received a cardiac diagnosis. Follow-up genetic testing was low (26%), however did confirm pathogenic mutations in three cases. CONCLUSION: Idiopathic VF is a rare diagnosis with a relatively good prognosis provided ICD therapy is initiated. Routine clinical follow-up is recommended due to potential late emerging cardiac pathology. ECG changes are common, but have no prognostic value in determining the risk of ventricular arrhythmias recurrence. Screening for genetic diseases has previously been low, and this calls for improvement, especially since cheaper and more comprehensive genetic panels are now readily available.

From uncertainty to gradually managing and awaiting recovery of a periodic condition- a qualitative study of parents´ experiences of PFAPA syndrome.

BACKGROUND: The prevalence of periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis (PFAPA) syndrome is unknown. Although an uncommon condition, it is considered to be the most common autoinflammatory disease among children in many parts of the world. The knowledge of the consequences of the recurrent fever episodes for the child and its family are limited. This study explores the experiences of parents regarding the impact of the disease on the child's general well-being, the family's situation and how the family handles the associated challenges. METHODS: A qualitative approach was used, applying a modified version of Grounded theory for design, data collection and analysis. Data was collected from two different sources: communication between parents of children with PFAPA in a closed Facebook group and face-to face interviews with one of the parents of children diagnosed with PFAPA (6 mothers and 2 fathers). RESULTS: Parents described a lengthy process of how everyday life becomes affected by their child's recurrent fever episodes. This process is depicted in the following Grounded Theory core category: From uncertainty to gradually managing and awaiting recovery. The categories Uncertainty, Assurance, Gradually managing and Recovery describe the experienced illness trajectory. The illness representation illustrates the experiences/impacts of the periodic condition in the subcategories: Harmlessness-Severity, Disclosure of diagnosis, Impact on daily life and Regularity-Unpredictability. The children's well-being was highly affected by the symptoms during episodes. Parents experienced increased stress with constant fatigue, social constraints of family life and restricted career opportunities. Nevertheless, hope of recovery was constantly present. CONCLUSIONS: PFAPA is associated with a considerable burden on the child and the parents in daily life. Obtaining a diagnosis enables parents to move from a state of uncertainty towards a sense of coherence while awaiting recovery. Because of limited general knowledge of the condition and its impact on daily life, health care professionals need to become aware of the parents' efforts to mitigate the consequences of the recurrent episodes for the child and for the family as a whole.

Definitions, measurements and prevalence of fear of childbirth: a systematic review.

BACKGROUND: Fear of Childbirth (FOC) is a common problem affecting women's health and wellbeing, and a common reason for requesting caesarean section. The aims of this review were to summarise published research on prevalence of FOC in childbearing women and how it is defined and measured during pregnancy and postpartum, and to search for useful measures of FOC, for research as well as for clinical settings. METHODS: Five bibliographic databases in March 2015 were searched for published research on FOC, using a protocol agreed a priori. The quality of selected studies was assessed independently by pairs of authors. Prevalence data, definitions and methods of measurement were extracted independently from each included study by pairs of authors. Finally, some of the country rates were combined and compared. RESULTS: In total, 12,188 citations were identified and screened by title and abstract; 11,698 were excluded and full-text of 490 assessed for analysis. Of these, 466 were excluded leaving 24 papers included in the review, presenting prevalence of FOC from nine countries in Europe, Australia, Canada and the United States. Various definitions and measurements of FOC were used. The most frequently-used scale was the W-DEQ with various cut-off points describing moderate, severe/intense and extreme/phobic fear. Different 3-, 4-, and 5/6 point scales and visual analogue scales were also used. Country rates (as measured by seven studies using W-DEQ with ≥85 cut-off point) varied from 6.3 to 14.8%, a significant difference (chi-square = 104.44, d.f. = 6, p < 0.0001). CONCLUSIONS: Rates of severe FOC, measured in the same way, varied in different countries. Reasons why FOC might differ are unknown, and further research is necessary. Future studies on FOC should use the W-DEQ tool with a cut-off point of ≥85, or a more thoroughly tested version of the FOBS scale, or a three-point scale measurement of FOC using a single question as 'Are you afraid about the birth?' In this way, valid comparisons in research can be made. Moreover, validation of a clinical tool that is more focussed on FOC alone, and easier than the longer W-DEQ, for women to fill in and clinicians to administer, is required.

Person-centred, web-based support in pregnancy and early motherhood for women with Type 1 diabetes mellitus: a randomized controlled trial.

AIMS: To report results from and explore use of a multicentre, parallel-group, unblinded, randomized controlled trial testing the effectiveness in terms of well-being and diabetes management of a person-centred, web-based support programme for women with Type 1 diabetes, in pregnancy and postpartum. METHODS: Between 2011 and 2014, 174 pregnant women with Type 1 diabetes were randomly allocated (1:1) to web-based support and standard care (intervention group, n=83), or standard care (control group, n=91). The web-based support consisted of evidence-based information; a self-care diary for monitoring of daily activities; and peer support in a discussion forum. The primary outcomes (mean difference, measured at 6 months after childbirth) were well-being and diabetes management. RESULTS: No differences were found with regard to the primary outcome measure scores for general well-being [1.04 (95% CI -1.28 to 3.37); P=0.68] and self-efficacy of diabetes management [0.08 (95% CI -0.12 to 0.28); P= 0.75], after adjustment for baseline differences in the insulin administration method, nor with regard to the secondary outcome measures. CONCLUSIONS: At 6 months after childbirth, the web-based support plus standard care was not superior to standard care in terms of general well-being or self-efficacy of diabetes management. This might be explained by the low number of participants who had a high activity level. Few simultaneously active participants in the web-based programme and stressors in motherhood and diabetes postpartum were the main barriers to its use. Further intervention studies that offer web-based support are needed, with lessons learned from the present study. (Clinicaltrials.gov identification number: NCT015665824).

A tortuous route to a capable fatherhood: the experience of being a father to a child with severe haemophilia.

INTRODUCTION: Haemophilia is a chronic illness that affects the whole family as the child's reactions to the illness occur in interaction with the parents. Limited research has been conducted on how fathers of children with haemophilia experience their life situation. AIM: The aim of this study was to describe the lived experience of being a father to a child with severe haemophilia. METHOD: Individual, qualitative interviews were conducted with 14 fathers of 17 children with severe Haemophilia A. Data were analysed by means of a phenomenological hermeneutic method, including naïve reading, structural analysis and comprehensive interpretation. RESULTS: The results revealed that the fathers gradually grew into fatherhood through a process that can be explained in the metaphor, 'A tortuous road to a capable fatherhood'. The fathers experienced sorrow, powerlessness, concern and loss of a regular fatherhood after the child's diagnosis. The loss of an envisaged fatherhood emerged as the greatest sorrow of being a father to a child with haemophilia. When home treatment with factor concentrates functioned without the involvement of Health Care Personal (HCP), the fathers' sense of insufficiency decreased. CONCLUSION: A sense of being a capable father was associated with a sense of independence and control of one's life situation. Support from the Haemophilia Treatment Centre (HTC) in the learning process is essential for both parents of a child with severe haemophilia. Awareness of the fathers' struggle to feel capable is also vital while supporting the family in the first years after diagnosis.

Novel mutation in the KCNJ2 gene is associated with a malignant arrhythmic phenotype of Andersen-Tawil syndrome.

BACKGROUND: Andersen-Tawil syndrome (ATS) is a rare inherited multisystem disorder associated with mutations in KCNJ2 and low prevalence of life-threatening ventricular arrhythmias. Our aim was to describe the clinical course of ATS in a family, in which the proband survived aborted cardiac arrest (ACA) and genetic screening revealed a previously unknown mutation (c.271_282del12[p.Ala91_Leu94del]) in the KCNJ2 gene. METHODS: A cascade family screening was performed in a 5-generation family after identification of the KCNJ2 mutation in the proband. Subsequently, 10 of 21 screened individuals appeared to be mutation carriers (median age 38 [range 10-75] years, 3 female). Mutation carriers underwent clinical examination including biochemistry panel, cardiac ultrasound, Holter ECG, and exercise stress test. RESULTS: (1) At baseline, 2 patients had survived ACA, 3 had syncope or presyncopal attacks, and 2 reported palpitations. Exercise-induced nonsustained bidirectional ventricular tachycardia was documented in 4 patients, 2 received implantable cardioverter-defibrillators (ICD) for primary prevention and 2 for secondary prevention. (2) During follow-up, 1 primary prevention and 1 secondary prevention patient received in total 4 adequate ICD shocks. Life-threatening ventricular arrhythmias were documented during childhood in 5 of 10 mutation carriers. (3) All mutation carriers presented with characteristic mild dysmorphic features. Only 1 patient suffered from periodic paralysis. All had normal serum potassium level at repeated assessments and none had any other extracardiac disease manifestation. CONCLUSION: Our findings suggest that the novel KCNJ2 mutation is associated with a predominantly cardiac phenotype of Andersen-Tawil syndrome with high propensity to life-threatening ventricular arrhythmias presenting from childhood and young adulthood.

Reefs and islands of the Chagos Archipelago, Indian Ocean: why it is the world's largest no-take marine protected area.

The Chagos Archipelago was designated a no-take marine protected area (MPA) in 2010; it covers 550 000 km2, with more than 60 000 km2 shallow limestone platform and reefs. This has doubled the global cover of such MPAs.It contains 25-50% of the Indian Ocean reef area remaining in excellent condition, as well as the world's largest contiguous undamaged reef area. It has suffered from warming episodes, but after the most severe mortality event of 1998, coral cover was restored after 10 years.Coral reef fishes are orders of magnitude more abundant than in other Indian Ocean locations, regardless of whether the latter are fished or protected.Coral diseases are extremely low, and no invasive marine species are known.Genetically, Chagos marine species are part of the Western Indian Ocean, and Chagos serves as a 'stepping-stone' in the ocean.The no-take MPA extends to the 200 nm boundary, and. includes 86 unfished seamounts and 243 deep knolls as well as encompassing important pelagic species.On the larger islands, native plants, coconut crabs, bird and turtle colonies were largely destroyed in plantation times, but several smaller islands are in relatively undamaged state.There are now 10 'important bird areas', coconut crab density is high and numbers of green and hawksbill turtles are recovering.Diego Garcia atoll contains a military facility; this atoll contains one Ramsar site and several 'strict nature reserves'. Pollutant monitoring shows it to be the least polluted inhabited atoll in the world. Today, strict environmental regulations are enforced.Shoreline erosion is significant in many places. Its economic cost in the inhabited part of Diego Garcia is very high, but all islands are vulnerable.Chagos is ideally situated for several monitoring programmes, and use is increasingly being made of the archipelago for this purpose.

Increased circulating levels of basement-membrane components in patients with abdominal aortic aneurysms--a pilot study.

AIM: The decision for abdominal aortic aneurysm (AAA) repair is based on aneurysm size. However, smaller aneurysms can rupture, while larger ones can remain stable. New variables and markers are needed to better select patients at high rupture risk. The study was done to analyse if AAA patients have increased levels of circulating basement-membrane (BM) fragments. DESIGN: Circulating levels of BM components type IV and XVIII collagen were measured by enzyme-linked immunosorbent assay (ELISA) in 10 patients with AAA, nine patients with peripheral artery disease (PAD) and 10 healthy controls (CON). RESULTS: AAA patients had significantly increased levels of type IV and XVIII collagen compared with CON (134.0 ± 24.8 ng ml(-1) vs. 104.5 ± 16.4 ng ml(-1); p = 0.005 and 149.0 ± 56.9 ng ml(-1) vs. 59.6 ± 8.7 ng ml(-1); p < 0.001, respectively). The PAD patients did not have significantly increased levels of these fragments when compared with CON. In addition, the AAA patients had significantly increased level of type XVIII collagen (149.0 ± 56.9 ng ml(-1) vs. 58.3 ± 25.4 ng/ml(-1); p < 0.01) when compared with the PAD group. CONCLUSION: Based on this preliminary analysis of a small number of subjects, patients with AAA had significantly increased levels of circulating BM components. BM fragments should be studied further to establish their potential role as biomarkers for AAA.

Type IV collagen is a tumour stroma-derived biomarker for pancreas cancer.

BACKGROUND: Pancreas cancer is a dreaded disease with high mortality, despite progress in surgical and oncological treatments in recent years. The field is hampered by a lack of good prognostic and predictive tumour biomarkers to be used during follow-up of patients. METHODS: The circulating level of type IV collagen was measured by ELISA in pancreas cancer patients and controls. The expression pattern of type IV collagen in normal pancreas, pancreas cancer tissue and in pancreas cancer cell lines was studied by immunofluorescence and Western blot techniques. RESULTS: Patients with pancreas cancer have significantly increased circulating levels of type IV collagen. In pancreas cancer tissue high levels of type IV collagen expression was found in close proximity to cancer cells in the tumour stroma. Furthermore, pancreas cancer cells were found to produce and secrete type IV collagen in vitro, which in part can explain the high type IV collagen expression observed in pancreas cancer tissue, and the increased circulating levels in pancreas cancer patients. Of clinical importance, our results show that the circulating level of type IV collagen after surgery is strongly related to prognosis in patients treated for pancreas cancer by pancreatico-duodenectomy with curative intent. Persisting high levels of circulating type IV collagen after surgery indicates a quick relapse in disease and poor survival. CONCLUSION: Our results most importantly show that stroma related substances can be evaluated as potential cancer biomarkers, and thereby underline the importance of the tumour microenvironment also in this context.

Glycaemic control and diabetes care utilization in young adults with Type 1 diabetes.

OBJECTIVES: To explore how glycaemic control in young adults is related to diabetes care utilization during the transition to adult diabetes care and if these variables differ between males and females. METHODS: This is a retrospective, longitudinal design following patients' records from age 18-24 years. Adolescents (n = 104) connected to one paediatric outpatient clinic and referred to six different adult clinics were included. Data were collected regarding gender, age at diagnosis and transfer, yearly glycated haemoglobin (HbA(1c)) and body mass index, severe hypoglycaemia and diabetic ketoacidosis, retinopathy and diabetes care utilization. RESULTS: HbA(1c) decreased over time in females (P = 0.004) but not in males. Less than 10% had HbA(1c) in the recommended range during the study period. The decrease in severe hypoglycaemia and diabetic ketoacidosis was not significant. The prevalence of background retinopathy increased from 5 to 29% during the study period (P < 0.001). Mean transfer age was 19.8 years. The youths visited the paediatric clinic more often than the adult clinic (P < 0.001) and females visited adult care more often than males (P = 0.04). There was a steady decrease in the number of visits/year over time (P < 0. 001). Poor glycaemic control was associated with more visits for both males and females (P = 0.005) in adult care. CONCLUSIONS: As there was no gender difference in the relation between HbA(1c) and the number of visits in adult diabetes care, the higher frequency of visits in adult care for females cannot be solely explained by their glycaemic control. Gender differences regarding diabetes care utilization should be further explored.

Tiling resolution array CGH of dic(7;9)(p11 approximately 13;p11 approximately 13) in B-cell precursor acute lymphoblastic leukemia reveals clustered breakpoints at 7p11.2 approximately 12.1 and 9p13.1.

The dic(7;9)(p11 approximately 13;p11 approximately 13) is a recurrent chromosomal abnormality in acute lymphoblastic leukemia (ALL), mainly of B-lineage. Although more than 20 dic(7;9)-positive ALLs have been reported to date, the molecular genetic consequences of this aberration are unknown. We performed tiling resolution (32K) genome-wide array-based comparative genomic hybridization (array CGH) analysis of three cases with dic(7;9) in order to characterize the breakpoints on 7p and 9p. The analysis showed a clustering of breakpoints within 9p13.1 in all three cases and within 7p11.2 in two cases; the array CGH revealed two different breakpoints - 7p12.1 and 7p14.1 - in the remaining case. Based on these findings the abnormality should hence be designated dic(7;9)(p11.2 approximately 12.1;p13.1). Locus-specific fluorescence in situhybridization analysis of one of the cases narrowed down the 7p11.2 breakpoint to a <500-kb segment in this sub-band, a region containing three known genes. Unfortunately, lack of material precluded further molecular genetic studies, and it thus remains unknown whether the pathogenetically important outcome of the dic(7;9) is formation of a chimeric gene or loss of 7p and/or 9p material.

Remote treatment of bulimia nervosa and binge eating disorder: a randomized trial of Internet-assisted cognitive behavioural therapy.

The present study investigated the efficacy of self-help based on cognitive behaviour therapy in combination with Internet support in the treatment of bulimia nervosa and binge eating disorder. After confirming the diagnosis with an in-person interview, 73 patients were randomly allocated to treatment or a waiting list control group. Treated individuals showed marked improvement after 12 weeks of self-help compared to the control group on both primary and secondary outcome measures. Intent-to-treat analyses revealed that 37% (46% among completers) had no binge eating or purging at the end of the treatment and a considerable number of patients achieved clinically significant improvement on most of the other measures as well. The results were maintained at the 6-month follow-up, and provide evidence to support the continued use and development of self-help programmes.

Prevention of ischaemia-induced small intestinal adhesions in foals.

REASONS FOR PERFORMING STUDY: Treatments addressing variously theorised pathophysiological mechanisms of small intestinal adhesions have been reported. This study applied those classes of treatments to the most clinically relevant aetiology of post operative adhesions. HYPOTHESIS: Treatments addressing the pathophysiology of ischaemia-reperfusion induced adhesions would accordingly reduce the incidence of adhesions from this model. METHODS: Four classes of treatments were administered for 72 h to 16 foals subjected to complete ischaemia followed by reperfusion to create peritoneal adhesions. These groups were: 1) FPG group--flunixin meglumine (1.1 mg/kg bwt i.v., divided q.i.d.), potassium penicillin G (22,000 iu/kg bwt i.v., q.i.d.) and gentamicin (2.2 mg/kg bwt i.v., t.i.d.); 2) HEP group--heparin (80 iu/kg bwt subcut., b.i.d.); 3) DMSO group--dimethylsulphoxide (DMSO) (20 mg/kg bwt [diluted in 500 ml normal saline] i.v., b.i.d.); and 4) SCMC group--sodium carboxymethylcellulose (500 ml 3% sterile solution intraperitoneally, administered only at the beginning of surgery). RESULTS: Post operative intestinal obstruction did not occur in any foal. After 10 days, necropsy revealed bowel-to-bowel adhesions in none of the FPG or DMSO groups, in 2/4 of the SCMC group, in 3/4 of the HEP group and 5/6 foals subjected to the procedure without treatment (UIR group). CONCLUSIONS: Inhibition of the inflammation associated with ischaemia and reperfusion in foals treated with FPG or DMSO decreased small intestinal adhesions in foals. POTENTIAL RELEVANCE: Although anti-inflammatory therapy was shown to eliminate bowel-bowel adhesions in this controlled study, it must be remembered that clinical cases are without control. These therapies are advised to improve the result but are unlikely to eliminate the problem.

DNA double-strand breaks associated with replication forks are predominantly repaired by homologous recombination involving an exchange mechanism in mammalian cells.

DNA double-strand breaks (DSB) represent a major disruption in the integrity of the genome. DSB can be generated when a replication fork encounters a DNA lesion. Recombinational repair is known to resolve such replication fork-associated DSB, but the molecular mechanism of this repair process is poorly understood in mammalian cells. In the present study, we investigated the molecular mechanism by which recombination resolves camptothecin (CPT)-induced DSB at DNA replication forks. The frequency of homologous recombination (HR) was measured using V79/SPD8 cells which contain a duplication in the endogenous hprt gene that is resolved by HR. We demonstrate that DSB associated with replication forks induce HR at the hprt gene in early S phase. Further analysis revealed that these HR events involve an exchange mechanism. Both the irs1SF and V3-3 cell lines, which are deficient in HR and non-homologous end joining (NHEJ), respectively, were found to be more sensitive than wild-type cells to DSB associated with replication forks. The irs1SF cell line was more sensitive in this respect than V3-3 cells, an observation consistent with the hypothesis that DSB associated with replication forks are repaired primarily by HR. The frequency of formation of DSB associated with replication forks was not affected in HR and NHEJ deficient cells, indicating that the loss of repair, rather than the formation of DSB associated with replication forks is responsible for the increased sensitivity of the mutant strains. We propose that the presence of DSB associated with replication forks rapidly induces HR via an exchange mechanism and that HR plays a more prominent role in the repair of such DSB than does NHEJ.

Cytogenetic changes in benign proliferative and nonproliferative lesions of the breast.

Cytogenetic analysis of short-term cultures from 69 cases of fibrocystic breast changes and 10 samples of normal mammary tissue revealed clonal chromosome aberrations in six fibrocystic lesions. All the histologically normal tissue samples had a normal karyotype. The frequency of cytogenetically abnormal cases seems to correlate with the degree of histopathologic changes of the tissue; nonproliferative lesions may have clonal chromosome alterations, but at a low frequency. Whether women with karyotypically altered fibrocystic "disease" have a higher risk of developing invasive breast cancer, compared with women without microscopically visible genetic anomalies in fibrocystic lesions, remains unknown.

Cytogenetics of benign breast lesions.

This review summarizes the cytogenetic information on benign breast lesions of various histologies, i.e., fibrocystic lesions from women with and without a known hereditary predisposition to breast cancer, fibroadenomas, phyllodes tumors, and papillomas, and relate the chromosomal features with those in breast carcinoma. In general, the frequency of chromosome abnormalities is lower in benign lesions than in breast cancer, and seems to correlate with the histologic features of the tissue, and the corresponding risk of developing invasive mammary carcinoma; aberrations are more common in proliferative than in nonproliferative lesions. The karyotypes are generally less complex than those detected in invasive carcinoma, and more often involve balanced rearrangements. No lesion-specific aberration has so far been detected; on the contrary, changes repeatedly encountered in breast cancer samples can be found in benign lesions as well, e.g., gain of 1q, interstitial deletion of 3p, and trisomies 7, 18, and 20. Especially intriguing is the prevalence of rearrangements of the short arm of chromosome 3, with the minimally deleted bands 3p13-14, in proliferative lesions from prophylactic mastectomies in breast cancer families. The potential tumor suppressor gene(s) in this region remains, however, to be identified.