Effects of tamoxifen on normal breast tissue histological composition: Results from a randomised six-arm placebo-controlled trial in healthy women

Tamoxifen prevents recurrence of breast cancer and is suggested for preventive risk-reducing therapy. Tamoxifen reduces mammographic density, a proxy for therapy response, but little is known about its effects in remodelling normal breast tissue. Our study, a substudy within the double-blinded dose-determination trial KARISMA, investigated tamoxifen-specific changes in breast tissue composition and histological markers in healthy women. We included 83 healthy women randomised to 6 months daily intake of 20, 10, 5, 2.5, 1 mg of tamoxifen or placebo. The groups were combined to “no dose” (0-1 mg), “low-dose” (2.5-5 mg) or “high-dose” (10-20 mg) of tamoxifen. Ultrasound-guided biopsies were collected before and after tamoxifen exposure. In each biopsy, epithelial, stromal and adipose tissues was quantified, and expression of epithelial and stromal Ki67, oestrogen receptor (ER) and progesterone receptor (PR) analysed. Mammographic density using STRATUS was measured at baseline and end-of-tamoxifen-exposure. We found that different doses of tamoxifen reduced mammographic density and glandular-epithelial area in premenopausal women and associated with reduced epithelium and increased adipose tissue. High-dose tamoxifen also decreased epithelial ER and PR expressions in premenopausal women. Premenopausal women with the greatest reduction in proliferation also had the greatest epithelial reduction. In postmenopausal women, high-dose tamoxifen decreased the epithelial area with no measurable density decrease. Tamoxifen at both low and high doses influences breast tissue composition and expression of histological markers in the normal breast. Our findings connect epithelial proliferation with tissue remodelling in premenopausal women and provide novel insights to understanding biological mechanisms of primary prevention with tamoxifen.     

Fricke supraorbital flap for reconstruction of total lower eyelid defects

Summary Split or full thickness eyelid defects resulting from tumor destruction or surgical excision present a dilemma for plastic and reconstructive surgeons. Full thickness eyelid replacement requires composite grafting of the skin, together with tarsal support of its substitute and mucosa. The flap described by Fricke in 1829 was used for reconstruction of anterior lamella in six lower eyelid defects. In three of our cases chondromucosal grafts taken from nasal septum were utilized for posterior lamella repair. The results have been satisfactory from a functional and cosmetic standpoint.     

Acute leukaemia in a defined geographic area – Incidence,clinical history and prognosis

A consecutive series of patients (1978–1981) comprising all patients with acute leukaemia from a population of 475000 inhabitants was reviewed. Thus, 94 patients were diagnosed as having acute leukaemia. No patients were lost from follow-up. The incidence figures of ALL and AML differed significantly from those of Sweden as a whole. 9 patients were < 15 years old. The median age of adult patients was 64 years, 60.8% being ≥ 60 years old. Of adult patients with AML, 20% had a preleukaemic history (chronic myeloproliferative disorders, myelodysplastic syndromes and others). None of 6 patients with leukaemia as a metamorphosis of a chronic myeloproliferative disorder achieved a complete remission. The overall remission rate of the remaining adult patients was 25%. Treated patients, 15–39 years old, with AML without any preleukaemic history, had a complete remission rate of 80% compared to 12% for patients ≥ 60 years old with the same diagnosis. Of 60 patients with ‘primary’ AML, 14 were not treated, mainly because of advanced age and complicating diseases. Most of these patients died within a week of admission.     

Treatment of horizontal root‐fractured maxillary incisors – a case report

Abstract – Traumatic dental injuries often occur to the teeth and their supporting tissues and they are the main reasons for emergency visit to a dental clinic. Management of a fracture depends on its position and the extent of root involvement. Horizontal root fractures are not seen frequently and the treatment consists of reduction and long‐term rigid fixation of the coronal segment. The present case demonstrates the successful management of two horizontally fractured maxillary central incisors with a follow‐up period of 9 months.     

Sequential bilateral germ cell tumours of the testis

Bilateral germ cell tumours of the testis are rare but a rise in their incidence is expected since with the new therapeutic possibilities a significant improvement in prognosis has been achieved even in patients with advanced metastatic spread. Of the 210 patients treated for malignent germ cell tumours at our Department, six (2.9%) developed a contralateral testicular tumour. All patients had metachronous tumours and the second tumours occurred after an interval ranging between 1 and 22 years. The epidemiology, histology, diagnosis, therapy and prognosis are discussed, and the significance of regular self-examination of the remaining testis in patients with testicular tumour is emphasized.     

Effects of Dopamine D1 and D2 Receptor Agonists and Antagonists on Seizures Induced by Chemoconvulsants in Mice

Abstract: Dopamine agonists and antagonists with different affinities for D₁ and D₂ receptors in the brain were assessed for their ability to affect clonic seizures in mice induced by chemoconvulsants. The dopamine D₂ antagonists remoxipride (5-20 mg/kg) and raclopride (5-20 mg/kg), haloperidol (2.5 and 5 mg/kg) and the D₁ antagonist SCH 23390 (0.3, 1.5 mg/kg) did not markedly modify seizures induced by pentylenetetrazole, picrotoxin or bicuculline. The dopamine D₂ agonist quinpirole only weakly blocked the action of pentylenetetrazole while the D₁ agonist SKF 38393 (1-10 mg/kg subcutaneously) caused a dose-dependent blockade of pentylenetetrazole-induced seizures. The D₁/D₂ agonist apomorphine given at “postsynaptic” doses (1 and 2 mg/kg) blocked pentylenetetrazole-induced seizures. The protection afforded by apomorphine against pentylenetetrazole seizures appeared to be associated with its activation of both D₁ and D₂ receptors since both raclopride and SCH 23390 blocked the action of apomorphine. Reserpine and the two partial dopamine autoreceptor agonists, (—)3-PPP and HW-165, at high (non-autoreceptor selective) doses induced seizures in animals treated with the subconvulsive dose of pentylenetetrazole. The overall results suggest that dopamine receptor blockade has a minor or limited effect on seizures caused by GABA inhibition. The anticonvulsant effect of dopamine agonists such as apomorphine appears to be mediated by postsynaptic dopamine D₁ and D₂ receptors. Stimulation of dopamine D₁ receptors can reduce seizure activity caused by GABA receptor blockade possibly by facilitation of GABA transmission in the striatum and substantia nigra.     

Glucose concentration in the vitreous of nondiabetic and diabetic human eyes

Glycation (nonenzymatic glucosylation) of collagen may play a role in the primary pathology of the vitreous in diabetes. The extent of glycation is determined by the glucose concentration in the tissue. In this study glucose concentration was assayed in blood and vitreous samples obtained from three patient groups undergoing vitrectomy: nondiabetic patients (ND), diabetic patients with insulin-dependent diabetes mellitus (IDDM) and diabetic patients with non-insulin-dependent diabetes mellitus (NIDDM). In the ND group the glucose concentration in the vitreous (3.5 +- 1.8 mM/1) was always lower than in the blood (9.1 +- 3.5 mM/1). In the diabetic groups the vitreous glucose concentration was, with a few exceptions, generally lower than the blood glucose concentration. The vitreous glucose concentration in these groups was generally higher (IDDM 9.4+-3.3 mM/1, NIDDM 7.2+-3.9 mM/1) than in the ND group, and in 15 specimens exceeded 11 mM/1, a level increasing the probability of collagen glycation in the vitreous of diabetic patients.This study was given financial support by the Herman Järnhardt Foundation, the Inez and Joel Carlsson Foundation and by Diabetesföreningen in Malmö     

004Topical Zinc Oxide for Open Pilonidal Wounds

Extended healing time and lack of documented effective treatments of sacrococcygeal pilonidal disease create substantial problems. Locally applied zinc oxide has been reported to promote wound healing. We have compared topical zinc oxide (3%) with placebo meshes for pilonidal wounds healing by secondary intention in a randomized, double‐blind, placebo‐controlled multicenter trial. Sixty‐four consecutive patients, 53 males, aged between 18 and 60 years (median 26 years) with excised pilonidal wounds were centrally randomized to local zinc oxide (30 mg/g, n = 33) or to placebo (n = 31) mesh treatment. Patients were followed with strict recording of beneficial and harmful effects. The median healing times were 54 days (42–71 days, interquartile range, n = 33) for the zinc group and 62 days (55–82 days, n = 31) for the placebo group. This difference was not statistically different (p = 0.32). Based on Cox regression analysis initial wound volume influenced healing negatively (p = 0.016) while smoking (p = 0.011) was associated with faster wound healing. Significantly (p < 0.01) more placebo (n = 12) than zinc oxide‐treated patients (n = 3) needed antibiotics postoperatively. Although topical zinc oxide increased (p < 0.001) wound fluid zinc levels (1830 ± 405 μM, mean ± SEM) compared with placebo (3.1 ± 1.6 μM) serum‐zinc levels did not differ significantly between the zinc (13.5 ± 0.4 μM) and placebo (12.8 ± 0.4 μm) groups on postoperative day 7. No adverse events were recorded. Topical zinc oxide treatment did not accelerate time to closure of open pilonidal wounds but was associated with reduced antibiotic usage.