Gene amplification in ductal carcinoma in situ of the breast.

Multiple different biologically and clinically relevant genes are often amplified in invasive breast cancer, including HER2, ESR1, CCND1, and MYC. So far, little is known about their role in tumor progression. To investigate their significance for tumor invasion, we compared pure ductal carcinoma in situ (DCIS) and DCIS associated with invasive cancer with regard to the amplification of these genes. Fluorescence in situ hybridization (FISH) was performed on a tissue microarray containing samples from 130 pure DCIS and 159 DCIS associated with invasive breast cancer. Of the latter patients, we analyzed the intraductal and invasive components separately. In addition, lymph node metastases of 23 patients with invasive carcinoma were included. Amplification rates of pure DCIS and DCIS associated with invasive cancer did not differ significantly (pure DCIS vs. DCIS associated with invasive cancer: HER2 22.7 vs. 24.2%, ESR1 19.0 vs. 24.1%, CCND1 10.0 vs. 14.8%, MYC 11.8 vs. 6.5%; P > 0.05). Furthermore, we observed a high concordance of the amplification status for all genes if in situ and invasive carcinoma of individual patients were compared. This applied also to the corresponding lymph node metastases. Our results indicate no significant differences between the gene amplification status of DCIS and invasive breast cancer concerning HER2, ESR1, CCND1, and MYC. Therefore, our data suggest an early role of all analyzed gene amplifications in breast cancer development but not in the initiation of invasive tumor growth.

Symptomatic laryngeal nodular chondrometaplasia: a clinicopathological study.

A 41 year old man with a history of politrauma presented with a nodular mass of the left false vocal cord, associated with progressive dysphonia, dyspnoea, and dysphagia. A computed tomography scan of the neck region showed a rounded and circumscribed mass without infiltration of the surrounding tissues. Histological investigation of the nodule revealed the presence of fibroelastic cartilaginous tissue, surrounded by a thin rim of fibrous tissue, with rare hypercellular areas, occasional binucleated cells, slight hyperchromasia, and an irregular nuclear profile. Mitotic activity was absent. The patient's history of laryngeal trauma, with the subsequent progressive onset of clinical symptoms, helps to distinguish the chondrometaplastic nature of this nodule from true laryngeal cartilaginous tumours, such as chondroma and low grade chondrosarcoma.

Contraceptive knowledge and expectations by adolescents: an explanation by focus groups.

To determine the needs and expectations of adolescent girls concerning contraceptive use as well as their attitude to health care providers, a qualitative research was performed with four focus groups of 17-year-old girls of different education levels. All 26 girls except one were of Belgian origin. There was a fixed scenario for each group. The discussions were tape-recorded, transcribed and analysed via content analysis. Knowledge concerning the daily use and side-effects of contraceptives was insufficient. A school physician is not the person they want to talk to. The influence of the peer in the group is very important. The general practitioner is the most frequently consulted health care provider for the first pill prescription, but for a gynaecological examination they thought they had to visit a gynaecologist. The girls expected confidentiality from their general practitioner and wanted sufficient consultation time. Factors inhibiting the visits for obtaining contraceptives were the cost, waiting time and fear of the gynaecological examination. Adolescents intended to visit their general practitioner for contraceptives, but the family practice had to be easily accessible. It is a challenge for general practitioners to provide good contraceptives to adolescents and to promote compliance.

[Current treatment strategies for spondylodiscitis in surgical clinics in Germany]. / Aktuelle Behandlungsstrategien der Spondylodiszitis in deutschen Akutkliniken.

BACKGROUND: Spondylodiscitis is a rare disease which is associated with high mortality. No guidelines for treatment exist and the available studies are not homogeneous. Attempts have been made in recent years to structure therapy using algorithms. Early recognition of the disease is above all important for its later outcome. Therapy takes place in not only orthopaedic/trauma surgery clinics but also in neurosurgical clinics. MATERIAL AND METHOD: We sent an online survey on this subject to orthopaedic clinics, trauma surgery and neurosurgery clinics in Germany. The aim was to ascertain current care strategies in Germany. A further objective was to elicit differences between the specialist fields. RESULTS: A total of 164 clinics responded to the survey. The response rate was 16% of the orthopaedic/trauma surgery clinics and 32% of the neurosurgical clinics. Differences between the two specialist fields can be found particularly in the use of systemic and local antibiotics, in the choice of surgical access to the thoracic spine and the lumbar spine and in post-operative imaging. In both specialist fields, patients with neurological dysfunctions are treated primarily in clinics with high case numbers. In terms of surgery, 2/3 of the responding clinics choose a one-stage operative treatment. Minimally invasive procedures and the use of cages are widespread. The participants estimate that, on the whole, a better outcome and higher patient satisfaction tend to exist after operative treatment. CONCLUSIONS: The lack of homogeneity regarding treatment strategies which is indicated here clearly shows the need for therapy guidelines as an aid to orientation. This will be a challenge for the future due to the low incidence and the situation regarding currently available studies.

Antiestrogens, antiandrogens.

The aim of the study was to find new antiestrogenic and antiandrogenic structures. Out of the triphenyl-alkene derivatives Panomifene (EGIS-5660) proved to be the most active antiestrogenic compound which binds to specific estrogen receptors and exhibits inhibitory effects on experimental mammary tumors both in vitro and in vivo. The investigated antiandrogenic compounds were indol and imidazole derivatives. One of these compounds a di-imidazolil derivative, GYK1-24479 inhibited the in vitro androgen (testosterone and androstenedione) biosynthesis both in vitro and in vivo in concentration/dose dependent manner, and in these respects proved to be more active than the referent ketoconazole.

Hormonal changes during a prolonged tamoxifen treatment in patients with advanced breast cancer.

The effect of tamoxifen (TAM) on the serum levels of sexual hormones and on the sex hormone-binding globulin (SHBG) was investigated in 30 postmenopausal patients with advanced breast cancer. To study the 'prolactin reserve capacity' of the pituitary gland, thyrotrophin-releasing hormone (TRH) and sulpiride-induced prolactin release were measured prior to TAM treatment, then in the 2nd and 8th week of the therapy. The TRH (400 micrograms i.v.)-induced prolactin secretion was significantly suppressed by TAM after an 8-week treatment, but only in responding cases. Maximal prolactin stimulation occurred at the 15th min after TRH injection, being equal to 5,600 +/- 800 mlU/l in cancer patients, and decreasing to 2,400 +/- 150 mlU/l after 8 weeks. TAM did not suppress the sulpiride-inducable prolactin release either in responders or in nonresponders.

Antibiotics for coughing in general practice: a qualitative decision analysis.

BACKGROUND: In family practice, medical decisions are prompted most often by complaints about coughing. There is no single yardstick for the differential diagnosis of respiratory tract infections (RTIs). In 80% of cases, the excessive use of antibiotics in the treatment of RTIs is caused by the prescription behaviour of GPs. OBJECTIVE: Our aim was to explicate GPs' diagnostic (and therapeutic) decisions regarding adult patients who consult them with complaints about coughing, and to investigate what determines decision making. METHODS: Exploratory, descriptive focus groups were held with GPs. Hypotheses were generated on the basis of 'qualitative content analysis'. Results. Twenty-four GPs participated in four semi-structured group discussions. In order to differentiate RTIs from other possible diagnoses, less likely diagnoses were not ruled out explicitly. In the case of suspected RTI, there was a low degree of certainty in the differentiation between RTIs (e.g. between bronchitis and pneumonia). Clinical signs and symptoms, which determine the probability of disease, often left GPs with reasonable diagnostic doubt. In the end, the decision whether or not to prescribe antibiotics was taken. GPs' prescription behaviour was also determined by doctor- and patient-related factors (e.g. having missed pneumonia once, patient expectations). The 'chagrin factor' explains why these factors lead to a shift in the action threshold, in favour of antibiotics. CONCLUSION: This inductive research method enabled the generation of meaningful hypotheses regarding the complex decision processes pursued by GPs. The authors are developing an educational intervention that builds on these findings, focusing on the prescribing decision.

Action of thrombin on ovine, bovine and human pituitary growth hormones.

1. This communication reports the action of bovine thrombin on ovine, bovine and human growth hormones. Thrombin cleavage was shown to be restricted to a single homologous peptide bond in all three growth hormones (at sequence positions 133--134 of the ovine and bovine hormones). 2. Ovine growth hormone was the most sensitive to the action of thrombin, bovine growth hormone was attacked to a relatively less extent, and human growth hormone was the most resistant to the enzyme. 3. After reduction and carbamidomethylation of the disulfide bonds in thrombin modified ovine growth hormone, the two fragments (residues 1--133 and 134--191) were isolated. The large NH2-terminal thrombin fragment of the hormone (residues 1--133) was found to be inactive in the rat tibia test, whereas a tryptic fragment (residues 96--133) isolated in an independent way gave measurable responses.

An evaluation study of the didactic quality of clerkships.

CONTEXT: Previous qualitative research at the University of Antwerp revealed dissatisfaction amongst medical students about clinical clerkships. OBJECTIVE: To use quantitative methods to further explore student perceptions of their clinical teaching. METHOD, SAMPLE AND SETTING: Monthly questionnaire administered to final-year medical students at the University of Antwerp, Belgium. RESULTS: The response rate was 83.9%. Many of the qualitative findings were reproduced. Educational resources were not optimally used. The junior doctor was the most important clinical teacher. Many activities were passive experiences. Coaching, feedback and supervision associated most with general satisfaction of the clerkship, however, these dimensions were often considered suboptimal. CONCLUSIONS: Clinical clerkships do not automatically provide an ideal learning environment for medical students.

Discussing STIs: doctors are from Mars, patients from Venus.

BACKGROUND: Primary care plays an important role in promoting sexual health, but in this setting counselling regarding sexually transmitted infections (STIs) is rarely performed and often inadequate. OBJECTIVE: Our aim was to identify and quantify the barriers physicians encounter in discussing STIs with their patients. METHODS: A postal questionnaire-based survey was carried out in a random sample of 200 primary care physicians in Antwerp, Belgium. RESULTS: The response rate was 68%. Among the 122 respondents, only 44.3% provide some form of counselling (asking about sexual history, informing about safe sex or informing about STIs) regularly, at least once a week. Major barriers are language and comprehension problems (for 74.2% of respondents), ethnic differences (68.4%), insufficient training (69.4%), lack of time (60.8%), presence of the patient's partner (89.2%) or mother (94.2%), first contact with a patient (60.8%), fear of embarrassing the patient (30.6%) and a patient without genital complaints (71.4%). About half of the GPs fail to counsel an asymptomatic patient with obvious STI risk, and as many give no safe sex advice in a first contraception consultation. CONCLUSIONS: Physicians have many and various barriers to discussing STIs with their patients. Features of contemporary STI counselling and solutions to its problems are discussed. Education of health care providers should be given priority.

General practitioners caring for terminally ill patients resident in a hospice.

The goal of this study was to investigate why GPs have little or no involvement in the medical process relating to any of their patients when they are admitted to a palliative care unit (PCU) and what solutions they suggest. The study took the form of a descriptive pilot study based on a short questionnaire. It emerged that GPs felt their involvement was influenced by their job description, by practical factors (time investment, distance between practice and PCU, remuneration, referral) and personal issues (e.g. dealing with dying). It is concluded that GPs need education in palliative/supportive care and approved remuneration as well as knowledge about their task in the PCU.