Expression of cyclooxygenase-1 and cyclooxygenase-2, syndecan-1 and connective tissue growth factor in benign and malignant breast tissue from premenopausal women.

Stromal factors have been identified as important for tumorigenesis and metastases of breast cancer. From 49 premenopausal women, samples were collected from benign or malignant tumors and the seemingly normal tissue adjacent to the tumor. The factors studied, with real-time polymerase chain reaction (PCR) and immunohistochemistry, were cyclooxygenase-1 and cyclooxygenase-2 (COX-1 and COX-2), syndecan-1 (S-1) and connective tissue growth factor (CTGF). COX-1 and S-1 mRNA levels were higher in the malignant tumors than in normal and benign tissues. The COX-2 mRNA level was lower in the malignant tumor than in the normal tissue, while CTGF mRNA did not differ between the groups. COX-1 immunostaining was higher in stroma from malignant tumors than in benign tissues, whereas COX-2 immunostaining was higher in the malignant tissue. Glandular S-1 immunostaining was lower in malignant tumors compared to benign and normal tissues, and the opposite was found in stroma. Conclusively, mRNA levels of COX-1 and COX-2 were oppositely regulated, with COX-1 being increased in the malignant tumor while COX-2 was decreased. S-1 protein localization switched from glandular to stromal cells in malignant tissues. Thus, these markers are, in premenopausal women, localized and regulated differently in normal/benign breast tissue as compared to the malignant tumor.

Health-related quality of life during hormone therapy after breast cancer: a randomized trial.

AIM: To study the effects of menopausal hormone therapy (HT) on health-related quality of life in women after breast cancer. PATIENTS AND METHODS: In the Stockholm trial, breast cancer survivors were randomized to HT (estradiol and progestogen) or to a control group (no treatment). A subgroup of 75 women was studied (38 with HT, 37 controls). Fifty patients were on concomitant tamoxifen. Patients completed three questionnaires (EORTC QLQ C-30, EORTC QLQ-BR 23 and the Hospital Anxiety and Depression Scale (HADS)) during 1 year of treatment. RESULTS: A significant group-by-time interaction was found for improvement of insomnia in the HT group (p < 0.001). Within the HT group, but not in the control group, there was significant improvement for HADS anxiety, HADS depression, emotional, cognitive, and social functions and global quality of life. When HT was added to tamoxifen, the increase in global quality of life was significant (p < 0.01). CONCLUSION: The effects of HT on quality of life in breast cancer survivors have not previously been reported. The present data suggest that this controversial treatment may improve quality of life after breast cancer.

The shape of the metabolic memory of HbA1c: re-analysing the DCCT with respect to time-dependent effects.

AIMS/HYPOTHESIS: We determined the shape of the metabolic memory of HbA1c and its contribution to retinopathy, as well as the importance of reducing HbA1c to prevent progression of retinopathy. METHODS: The relative risk contribution of HbA1c values at different points in time to current progression of retinopathy was determined in the DCCT patients. RESULTS: HbA1c 2 to 3 years earlier had the greatest relative risk contribution to current progression of retinopathy. HbA1c up to 5 years earlier made a greater contribution than current values, while values from 8 years earlier still had an important impact. When HbA1c had been at 8% for a long period and was subsequently lowered to 7%, the salutary effects did not begin to appear until 2 to 3 years after lowering. The hazard function for a constant level of HbA1c increased with time. The numbers needed to treat when reducing HbA1c from 8.3% to 8% from diagnosis was estimated to be 1,688 for the first 3 years and 13 for the period 9 to 12 years. Survival functions when reducing HbA1c from 8% to 7% show that pre-study glycaemic control dominates the effect on progression of retinopathy during the first years of a trial. CONCLUSIONS/INTERPRETATION: The most harmful effect of hyperglycaemia on progression of retinopathy in type 1 diabetes initially increases, but declines after roughly 5 years. The salutary effect of reducing HbA1c accelerates with time and becomes greater in clinical practice than has been previously understood. Clinical trials should preferably be designed for long periods or include patients with low previous glycaemic exposure to distinguish trial effects from those of the metabolic memory.

Optimization of basal insulin delivery in Type 1 diabetes: a retrospective study on the use of continuous subcutaneous insulin infusion and insulin glargine.

AIMS: To compare the effects on glycaemic control after using continuous subcutaneous insulin infusion (CSII) or insulin glargine. METHODS: Data were obtained from 17 diabetes outpatient clinics in Sweden, employing the same diabetes data management system. Type 1 diabetic patients using multiple dose injections were included prior to starting on either CSII (n = 563) or glargine (n = 513). The median duration of therapy was 25 months for CSII and 6 months for glargine. The comparison between the treatment modalities was carried out by multiple regression analysis and logistic regression analysis in an attempt at reducing the influence of confounding factors. RESULTS: The mean HbA1c decrease was 0.59 +/- 1.19% for CSII and 0.20 +/- 1.07% for glargine (P < 0.001, when assessed by logistic regression). An additional 0.1% lower HbA1c would be expected if glargine had been optimized with basal insulin 40-60% of the daily dose. The more pronounced effect of CSII was achieved with a lower daily dosage of insulin. In a multiple regression analysis with a change of HbA1c as the dependent variable, the following variables were significant: choice of treatment (P < 0.001), HbA1c prior to treatment (P < 0.001) and BMI prior to treatment (P < 0.01). CONCLUSION: Both regimes improved metabolic control, but CSII resulted in significantly higher reduction in HbA1c than after insulin glargine treatment, particularly in those individuals who had higher levels of HbA1c at baseline.

Management and prognostic features of intracerebral hemorrhage during anticoagulant therapy: a Swedish multicenter study.

BACKGROUND AND PURPOSE: Patients treated with oral anticoagulants (ACs) have an increased risk of intracerebral hemorrhage (ICH), which is more often fatal than spontaneous ICH. Options to reverse the AC effect include intravenous administration of vitamin K, plasma, and coagulation factor concentrate. However, the optimal management of AC-related ICH has not been determined in any randomized trial. In this study, the present management of AC-related ICH was surveyed, and determinants of survival were assessed. METHODS: We retrospectively reviewed the medical records of all AC-related ICHs at 10 Swedish hospitals during a 4-year period, 1993 to 1996. Survival status after the ICH was determined from the Swedish National population register. RESULTS: We identified 151 patients with AC-related ICH. Death rates were 53.6% at 30 days, 63.6% at 6 months, and 77.5% at follow-up (mean 3.5 years). The case fatality ratio at 30 days was 96% among patients unconscious on admission (n=27), 80% among patients who became unconscious before active treatment was started (n=15), 55% among patients in whom no special action was taken except withdrawal of AC treatment (n=42), and 28% among patients given active anti-coumarin treatment while they were still conscious (n=64). The case fatality ratio at 30 days was 11% in the group treated with plasma (n=18), 30% in the group treated with vitamin K (n=23), and 39% in the group treated with coagulation factor concentrate (n=23). Within the first 24 to 48 hours after admission, 47% of the patients deteriorated. Choice of therapy to reverse the AC effect differed substantially between the hospitals (P<0.0001), as did the time interval from symptom onset to start of treatment. Multiple logistic regression analysis showed only 2 factors (intraventricular extension of bleeding and ICH volume) that were independently related to case fatality at both 30 days and 6 months. The results were similar when the analysis was restricted to patients who were conscious on admission. CONCLUSIONS: In AC-related ICH, a progressive neurological deterioration during the first 24 to 48 hours after admission is frequent, and the mortality is high. Choice of therapy to reverse the AC effect differed considerably between the hospitals. There was no evidence that any treatment strategy was superior to the others. A randomized controlled trial is needed to determine the best choice of treatment.

Waterhouse-Friderichsen syndrome and bilateral renal cortical necrosis in meningococcal sepsis.

Waterhouse-Friderichsen syndrome and bilateral renal cortical necrosis (BRCN) are rare complications of meningococcal sepsis associated with high mortality rates. We describe a 20-year-old man who presented with a 1-day history of fever, chills, malaise, and vomiting. He collapsed in the emergency room, requiring mechanical ventilation and intravenous vasopressors for resuscitation. He was noted to be anuric, and computed tomography showed adrenal hemorrhage and BRCN. Blood cultures later confirmed Neisseria meningitidis sepsis, and a biopsy confirmed renal cortical infarction. The patient was treated aggressively with intravenous antibiotics, corticosteroids, and immunoglobulins, in addition to plasmapheresis, dialysis, and supportive measures. He recovered his adrenal function and was discharged from the hospital, but he remains dialysis dependent. To our knowledge, this is the first reported case of concomitant Waterhouse-Friderichsen syndrome and BRCN in a patient with meningococcal sepsis.

Home monitoring of blood glucose and insulin therapy without a photometer.

The BM-Test-Glycemie 1-44 test strip facilitates self-monitoring without the use of a photometer. In a population of 33 diabetic patients (age 24.8 +/- 2.9 years) 94% took part in home monitoring for 6-10 months. Of 29 who answered a questionnaire 25 preferred blood glucose testing to urine testing. In a "beta-cell school" it was taught that it is rational if home monitoring of blood glucose is combined with a tailored insulin treatment consisting of long-acting insulin (Ultralente) as a basal insulin and regular insulin (Actrapid) as a meal insulin. In a group of 24 labile diabetic patients 17 preferred this regime compared to earlier use of intermediate acting insulin and regular insulin. Six of these preferred the regular insulin to be taken in three doses. Hypoglycemia, when it occurred, was less distressing in symptoms than previously. Among patients with recent onset of diabetes active participation with dose reduction was seen during the honey-moon stage. The regime is logical and generative, offers a basis for an individualized therapy and a high remission frequency may be expected.

Home monitoring of blood glucose without a photometer.

The ability to estimate blood glucose values at home is an important way of improving diabetic control. In order to investigate whether it was possible to replace the photometers used at present colour discrimination of ReflotestR-Glucose and ReflotestR-Hypoglycemie strips are studied. It was found that a colour scale could be used with one discrete shade of colour for each millimol between 1 to 20 millimol/l. A new test strip Haemo-GlukotestR 20-800 for colour scale usage was tested. Correlation with hexokinase method as reference was found to be r = 0.97.