Use of FreeStyle Libre Flash Monitor Register in the Netherlands (FLARE-NL1): Patient Experiences, Satisfaction, and Cost Analysis.

In patients with diabetes mellitus (DM), adequate glucose control is of major importance. When treatment schemes become more complicated, proper self-management through intermittent self-measurement of blood glucose (SMBG), among others, becomes crucial in achieving this goal. In the last decade, continuous glucose monitoring (CGM) has been on the rise, providing not only intermittent information but also information on continuous glucose trends. The FreeStyle Libre (FSL) Flash CGM system is a CGM system mainly used for patients with DM and is designed based on the same techniques as early CGMs. Compared with earlier CGMs, the FSL is factory calibrated, has no automated readings or direct alarms, and is cheaper to use. Although less accurate compared with the gold standard for SMBG, users report high satisfaction because it is easy to use and can help users monitor glucose trends. The Flash Monitor Register in the Netherlands (FLARE-NL) study aims to assess the effects of FSL Flash CGM use in daily practice. The study has a before-after design, with each participant being his or her own control. Users will be followed for at least 1 year. The endpoints include changes in HbA1c, frequency and severity of hypoglycemias, and quality of life. In addition, the effects of its use on work absenteeism rate, diabetes-related hospital admission rate, and daily functioning (including sports performance) will be studied. Furthermore, cost-benefit analysis based on the combination of registered information within the health insurance data will be investigated. Ultimately, the data gathered in this study will help increase the knowledge and skills of the use of the Flash CGM in daily practice and assess the financial impact on the use of the Flash CGM within the Dutch healthcare system.

Adult-onset congenital thrombotic thrombocytopenic purpura caused by a novel compound heterozygous mutation of the ADAMTS13 gene.

Thrombotic thrombocytopenic purpura (TTP) is a life-threatening disease, characterized by microangiopathic hemolytic anaemia and thrombocytopenia, resulting in neurologic and/or renal abnormalities. We report a 49-year-old patient with a history of thrombotic events, renal failure, and thrombocytopenia. Blood analysis demonstrated no ADAMTS13 activity in the absence of antibodies against ADAMTS13. The complete ADAMTS13 gene was sequenced, and two mutations were identified: one mutation on exon 24 (Arg1060Asp), which had previously been described, and a mutation on exon 27 (Met1260IlefsX34), which has not been reported. For these mutations, compound heterozygosity appears to be necessary to cause TTP, as family members of the patient display only one of the mutations and all displayed normal ADAMTS13 activity.

Hypercholesterolaemia and hepatosplenomegaly: two manifestations of cholesteryl ester storage disease.

Cholesteryl ester storage disease (CESD) is a rare autosomal recessive disease caused by mutations in LIPA. Here we describe two different clinical presentations of this disease: one case with a clear phenotype of familial hypercholesterolaemia and one case with hepatosplenomegaly from childhood onwards. These two cases exemplify the diversity of clinical phenotypes of patients with CESD. Knowledge on the phenotypic variability of the disease is of clinical relevance in light of enzyme replacement therapy (sebelipase alpha) for patients with mutations in LIPA, which is currently under development.

eGFR and creatinine clearance in relation to metabolic changes in an unselected patient population.

BACKGROUND: It is widely assumed that moderate to severe renal failure (creatinine clearance <60 ml/min; or an MDRD-4 (Modification of Diet in Renal Disease equation) <60 ml/min/1.73 m(2)) is associated with metabolic changes, often needing further assessment and treatment. We investigated whether such abnormalities are already present at earlier stages of kidney disease, as assessed by 24-hour urine sampling and MDRD-4 calculation. METHODS: A select, retrospective cohort study was conducted. Creatinine clearance was measured by collecting 24-hour urines. The individual eGFRs were calculated with the MDRD-4 formula and patients were then divided by renal function category (<15, 15-30, 30-45, 45-60, 60-90, >90 ml/min(/1.73 m(2))). Per clearance category the number of people with anaemia, hypokalaemia, uraemia and hyperphosphataemia was evaluated. RESULTS: The median creatinine clearance rate was 67.3 ml/min (quartiles: 42.9-95.8) versus a median MDRD-4-eGFR of 51.6 ml/min/1.73 m(2) (35.8-67.7). Anaemia, hyperkalaemia, hypocalcaemia, and uraemia were found to be present at higher levels of creatinine clearance rate and eGFR than previously reported (p<0.0005). This increased prevalence was more pronounced in elderly subjects, particularly with respect to anaemia (OR 2.71 and 2.02 for MDRD-4 and creatinine clearance respectively, p<0.0005). The same holds for the proportion with uraemia (OR 1.85, p<0.0005) and hypocalcaemia (OR 1.97, p=0.011) for MDRD-4. CONCLUSION: Metabolic changes in an in- and outpatient hospital population are present at earlier stages than was stated in recent guidelines, especially when creatinine clearance levels are used as indicators. This might have implications for testing and treatment of patients with suspected kidney disease and/or loss of renal function.

Antiproteinuric therapy decreases LDL-cholesterol as well as HDL-cholesterol in non-diabetic proteinuric patients: relationships with cholesteryl ester transfer protein mass and adiponectin.

OBJECTIVE: Dyslipidemia contributes to increased cardiovascular risk in nephrotic syndrome. We questioned whether reduction in proteinuria not only lowers low-density lipoprotein cholesterol (LDL-C), but also high-density lipoprotein cholesterol (HDL-C) and cholesteryl ester transfer protein (CETP) mass and whether changes in HDL-C were related to changes in plasma adiponectin. METHODS: Thirty-two non-diabetic proteinuric patients (12 on statin therapy), were followed during two double blind 6-week periods of placebo and treatment (low sodium + 100mg losartan + 25 mg hydrochlorothiazide). RESULTS: With placebo HDL-C was lower but LDL-C and CETP were not different in proteinuric patients compared with matched controls. LDL-C, HDL-C and CETP decreased upon proteinuria reduction. The decrease in LDL-C correlated with the drop in CETP and the degree of proteinuria reduction. HDL-C also decreased in proportion to proteinuria lowering. Individual changes in HDL-C were correlated with changes in adiponectin. CONCLUSION: LDL-C lowering upon robust reduction of proteinuria may be affected by changes in plasma CETP mass, but this treatment also decreases HDL-C in relation to the degree of proteinuria reduction. This adverse effect on HDL-C may in part be attributable to changes in adiponectin.

[Increase in orders for specific IgE tests and more positive results in children in 1985-2003]. / Meer aangevraagde tests op specifiek IgE bij kinderen in de loop van 1985-2003 en meer positieve uitslagen.

OBJECTIVE: To describe changes over time in the number of allergy tests for specific IgE ordered and outcomes in children, to help address the question whether the increase in allergies is due to an actual increase in sensitisation or an increase in diagnostic awareness of allergies among physicians. DESIGN: Retrospective and descriptive. METHOD: We reviewed the results of all specific IgE tests performed in our hospital's laboratory for children 0-18 years of age in the period 1985-2003. This included tests ordered by both general practitioners and hospital-based specialists. We analysed trends over time in the number of tests ordered (as an indicator ofdiagnostic awareness) and test results (as an indicator ofsensitisation). RESULTS: Between 1989 and 1995, the annual number of tests ordered increased from 1 per 10,000 children to 95 per 10,000 children and remained stable thereafter. Before 1990, more than 90% of tests were ordered by hospital-based specialists; after 1990, approximately 70% of the tests were ordered by general practitioners (p < 0.001). The proportion of positive tests remained stable at approximately 27% until 1991, after which it increased to more than 45% (p < 0.001). CONCLUSION: The increase in the proportion of positive tests suggests an increase in atopic sensitization between 1985 and 2000 which has stabilized since.

Results of the performance verification of the CoaguChek XS system.

BACKGROUND: This is the first paper reporting a performance verification study of a point-of-care (POC) monitor for prothrombin time (PT) testing according to the requirements given in chapter 8 of the International Organization for Standardization (ISO) 17593:2007 standard "Clinical laboratory testing and in vitro medical devices - Requirements for in vitro monitoring systems for self-testing of oral anticoagulant therapy". The monitor under investigation was the new CoaguChek XS system which is designed for use in patient self testing. Its detection principle is based on the amperometric measurement of the thrombin activity generated by starting the coagulation cascade using a recombinant human thromboplastin. METHODS: The system performance verification study was performed at four study centers using venous and capillary blood samples on two test strip lots. Laboratory testing was performed from corresponding frozen plasma samples with six commercial thromboplastins. Samples from 73 normal donors and 297 patients on oral anticoagulation therapy were collected. Results were assessed using a refined data set of 260 subjects according to the ISO 17593:2007 standard. RESULTS: Each of the two test strip lots met the acceptance criteria of ISO 17593:2007 versus all thromboplastins (bias -0.19 to 0.18 INR; >97% of data within accuracy limits). The coefficient of variation for imprecision of the PT determinations in INR ranged from 2.0% to 3.2% in venous, and from 2.9% to 4.0% in capillary blood testing. Capillary versus venous INR data showed agreement of results with regression lines equal to the line of identity. CONCLUSION: The new system demonstrated a high level of trueness and accuracy, and low imprecision in INR testing. It can be concluded that the CoaguChek XS system complies with the requirements in chapter 8 of the ISO standard 17593:2007.

Increased cholesterol efflux from cultured fibroblasts to plasma from hypertriglyceridemic type 2 diabetic patients: roles of pre beta-HDL, phospholipid transfer protein and cholesterol esterification.

We tested whether hypertriglyceridemia associated with type 2 diabetes mellitus is accompanied by alterations in pre beta-HDL, which are considered to be initial acceptors of cell-derived cholesterol, and by changes in the ability of plasma to promote cellular cholesterol efflux. In 28 hypertriglyceridemic and 56 normotriglyceridemic type 2 diabetic patients, and in 56 control subjects, we determined plasma lipids, HDL cholesterol and phospholipids, plasma pre beta-HDL and pre beta-HDL formation, phospholipid transfer protein (PLTP) activity, plasma cholesterol esterification (EST) and cholesteryl ester transfer (CET) and the ability of plasma to stimulate cholesterol efflux out of cultured human fibroblasts. HDL cholesterol and HDL phospholipids were lower, whereas plasma PLTP activity, EST and CET were higher in hypertriglyceridemic diabetic patients than in the other groups. Pre beta-HDL levels and pre beta-HDL formation were unaltered, although the relative amount of pre beta-HDL (expressed as % of total plasma apo A-I) was increased in hypertriglyeridemic diabetic patients. Cellular cholesterol efflux to plasma from hypertriglyceridemic diabetic patients was increased compared to efflux to normotriglyceridemic diabetic and control plasma, but efflux to normotriglyceridemic diabetic and control plasma did not differ. Multiple linear regression analysis demonstrated that cellular cholesterol efflux to plasma was positively and independently related to pre beta-HDL formation, PLTP activity and EST (multiple r=0.48), but not to the diabetic state. In conclusion, cholesterol efflux from fibroblasts to normotriglyceridemic diabetic plasma is unchanged. Efflux to hypertriglyceridemic diabetic plasma is enhanced, in association with increased plasma PLTP activity and cholesterol esterification. Unaltered pre beta-HDL formation in diabetic hypertriglyceridemia, despite low apo A-I, could contribute to maintenance of cholesterol efflux.

[Testing for specific immunoglobulins E (IgE) in case of suspected allergy in children: the results in a laboratory for general practitioners and medical specialists]. / Testen op specifieke immunoglobulinen E (IgE) bij vermoeden van allergie bij kinderen: resultaten in een laboratorium voor huisartsen en medisch specialisten.

OBJECTIVE: To describe the results of allergic sensitization tests to food and inhalant allergens in children younger than 4 years of age and in older children. DESIGN: Descriptive, retrospective. METHOD: The results of all specific IgE tests performed in children, 0-18 years ofage, in our hospital laboratory during the period 1985-2003 were reviewed. The hospital laboratory performed these tests for both general practitioners and specialists. RESULTS: During the study period, specific IgE tests were performed in 9131 children. Sensitization to inhalant allergens was found in 50% (3087/6185) of the children above 4 years of age and in 32% (9311/2946) of children 4 years of age or younger. Sensitization to house dust mite (12%), dog dander (9%), and cat dander (8%) was more common in young children than sensitization to pollen (7%) (p < 0.001). Sensitization to food allergens was found in 23% of schoolchildren and adolescents. Of these children, 48% were sensitized to 5 or more different inhalant or food allergens. In children 4 years of age or younger, paediatricians ordered most of the tests, while in the older children most tests were ordered by general practitioners. CONCLUSION: Sensitization to inhalant allergens is common in children 4 years of age or younger. Sensitization to food allergens is not confined to young children but is also frequently found in schoolchildren and adolescents. In such cases, there is often sensitization to several food and inhalant allergens, the clinical significance of which is usually unclear.

Troponin T elevation and prognosis after multivessel compared with single-vessel elective percutaneous coronary intervention.

BACKGROUND.: Although techniques for percutaneous coronary intervention (PCI) have improved, patients with PCI of more vessels may still have an increased risk. We performed a prospective observational study evaluating the differences between multivessel and single-vessel procedures according to postprocedural troponin T (TnT) elevation and events during follow-up. METHODS.: The study included 713 patients without elevated TnT (<0.05 ng/ml) before PCI. Primary endpoint was the combined endpoint of death, myocardial infarction, stroke, repeat coronary angiography and readmission for anginal symptoms during the mean follow-up of 10.9 months. RESULTS.: TnT after PCI was elevated in 150 patients (21%) and was significantly associated with an increased incidence of the primary endpoint (RR 1.55, 95% CI 1.01 to 2.38). PCI of more than one vessel was performed in 146 patients (20%). These patients more often had increased TnT levels after the procedure (31.5 vs. 18.3%, p=0.001) and an increased incidence of the primary endpoint during follow-up (28 vs. 19%, p=0.01). After multivariable analysis, multivessel PCI was a statistically significant predictor of postprocedural TnT increase (OR 1.90, 95% CI 1.17 to 3.06). Multivessel PCI was also associated with an increased risk of the primary endpoint (OR 1.73, 95% CI 1.18 to 2.52), but after adjusting for multivessel disease this association was not statistically significant (OR 1.42, 95% CI 0.92 to 2.19). CONCLUSION.: Elective PCI of more vessels in one session is, in comparison with single-vessel PCI, more often associated with postprocedural troponin T rise and a (nonsignificantly) higher incidence of cardiac events during follow-up. Whether staged PCI is associated with less morbidity has to be assessed. (Neth Heart J 2007;15:178-83.).

[Assessment of renal function according to the NHG protocol 'Diabetes mellitus type 2': risk of overestimating the number of diabetes patients with renal dysfunction]. / Bepaling van de nierfunctie volgens de NHG-standaard 'diabetes mellitus type 2': kans op overschatting van het aantal diabetespatiënten met nierfunctieproblemen.

OBJECTIVE: To evaluate the consequences of the new Dutch College of General Practitioners (NHG) protocol 'Diabetes mellitus type 2', which recommends using either the Cockcroft-Gault (CG) formula or the 'Modification of diet in renal disease' (MDRD) study formula to determine the estimated glomerular filtration rate (eGFR) as an indicator of renal function, in a cohort of patients with type-2 diabetes. DESIGN: Inventory. METHOD: The eGFR was calculated using the CG formula, the body-mass index (BMI-)corrected CG formula and the MDRD formula in 6224 patients with type-2 diabetes who entered the 'Zwolle outpatient diabetes project integrating available care' (ZODIAC) study in 2005. RESULTS: Using the CG and MDRD formulas, 31% and 63% of patients, respectively, had an eGFR of 30-59 ml/min (units for MDRD are ml/ min/1.73 m2) for which referral is advisable. In addition, 1% and 11%, respectively, had an eGFR <30 ml/min (reference: >90 ml/min), for which referral is necessary. Most patients aged >70 years (or > 50 years using the BMI-corrected CG formula) had an eGFR <60 ml/min. CONCLUSIONS: Reduced eGFR can be a sign of renal dysfunction but, using these formulas, can also be partly explained by advanced age. Therefore other factors should be considered when interpreting the results ofeGFR before it is concluded that the patient has kidney disease and the associated increased risk of cardiovascular disease.

Glucose dysregulation in nondiabetic patients with ST-elevation myocardial infarction: acute and chronic glucose dysregulation in STEMI.

BACKGROUND: Admission hyperglycaemia is associated with an increased risk of mortality after myocardial infarction. Whether long-term glucose dysregulation (assessed by HbA1c) is more important than acute hyperglycaemia is unknown. We evaluated the prognostic value of admission glucose and HbA1c levels in nondiabetic patients with ST-segment elevation acute myocardial infarction (STEMI). METHODS: In 504 unselected, consecutive patients with STEMI, glucose and HbA1c levels were measured on admission. Glucose was categorised as <11.1 mmol/l (n=422) and >or= 11.1 mmol/l (n=82). HbA1c levels were categorised as <6.0% (n=416) and >or=6.0% (n=88). Mean follow-up was 1.6+/-0.6 years. RESULTS: Patients with hyperglycaemia on admission were comparable with those with normoglycaemia. However,patients with HbA1c >or=6.0%, as compared with those with HbA1c <6%, were older, were more often on beta-blockers and more frequently had multivessel disease. Thirty-day mortality in the subsequent glucose categories (<11.1 mmol/l and >or=11.1 mmol/l) was 4% and 19% (p<0.001) and in the subsequent HbA1c categories (<6% and >or=6%) was 5% and 12% (p=0.03). After multivariable analyses, admission glucose (OR 4.91,95% CI 2.03 to 11.9, p< 0.001) but not HbA1c (OR 1.33, 95%CI 0.48 to 3.71, p=0.58) was significantly associated with 30-day mortality. Among 30-day survivors, neither admission glucose nor HbA1c were predictors of long-term mortality. CONCLUSION: Elevated admission glucose is an important predictor of 30-day outcome after STEMI, while prior long-term glucose dysregulation is a covariate of other high-risk clinical characteristics. Among 30-day survivors, neither admission blood glucose nor HbA1c were predictors of long-term outcome.

Effects of atorvastatin and vitamin E on lipoproteins and oxidative stress in dialysis patients: a randomised-controlled trial.

OBJECTIVES: The objective of this study was to examine the effects of treatment with atorvastatin, alpha-tocopherol and the combination of both, on lipoproteins and oxidative stress in dialysis patients. DESIGN AND SETTING: This double-blind randomised placebo-controlled trial was performed at the dialysis department of a non-university hospital. SUBJECTS, INTERVENTION AND MEASUREMENTS: A total of 44 clinically stable, non-diabetic patients on dialysis therapy (23 on haemo- and 21 on peritoneal-dialysis) without manifest cardiovascular disease were included in this study. They were randomised for treatment during a period of 12 weeks with 40 mg atorvastatin + placebo alpha-tocopherol (group 1) once daily, 800 IU alpha-tocopherol + placebo atorvastatin once daily (group 2), 40 mg atorvastatin + 800 IU alpha-tocopherol once daily (group 3), or placebo atorvastatin + placebo alpha-tocopherol once daily (group 4). Assessment of lipid profile and oxidative stress was performed at the start of the study and after 12 weeks of treatment. RESULTS: Treatment with atorvastatin reduced total cholesterol, triglycerides (TG), low-density lipoprotein (LDL) cholesterol, apolipoprotein B (apoB) and levels of oxidised LDL (oxLDL) with 30-43%. It had no influence on LDL oxidisability. Additional supplementation with alpha-tocopherol had no effect on lipid profile and oxLDL levels but decreased in vitro LDL oxidisability. No side-effects were observed. CONCLUSIONS: Treatment with atorvastatin is effective in lowering plasma total cholesterol, TG, LDL, apoB and oxLDL in a population of stable dialysis patients and might therefore be an effective tool in improving the poor cardiovascular outcome in these patients. Supplementation of alpha-tocopherol to atorvastatin had beneficial effects on in vitro LDL oxidisability and might therefore be of additional value. Further research on the clinical effects of treatment with atorvastatin in combination with alpha-tocopherol is necessary.

alpha-Tocopherol levels in plasma in new-onset, insulin-dependent diabetes mellitus.

BACKGROUND: Diabetic complications have been related to increased oxidative stress. Plasma antioxidant levels may be affected by hyperglycemia-induced oxidative stress as well as by insulin therapy. We evaluated the immediate effect of insulin treatment and improved metabolic control on the important antioxidant alpha-tocopherol plasma (vitamin E) levels in new-onset, insulin-dependent diabetes mellitus. METHODS: The study was performed in 15 consecutive patients, aged 20-67 years, with new-onset diabetes mellitus requiring acute insulin treatment. Plasma alpha-tocopherol levels were measured before the start of intensive insulin treatment and monthly for 6 months thereafter. Simultaneously, we studied plasma malondialdehyde (MDA) as a reflection of lipid peroxidation. In addition, comparisons were made to a nondiabetic reference group. RESULTS: Baseline alpha-tocopherol levels did not differ from those in nondiabetic subjects. alpha-Tocopherol decreased significantly, from 33.5+/-12.1 mumol/l before treatment to 28.11+/-6.85 mumol/l (-16%) after 1 month of insulin therapy (p<0.04) to 26.6+/-7.03 mumol/l (-20%) after 3 months of insulin therapy (p<0.02). This trend did not change after adjusting for variations in cholesterol levels. After 6 months, alpha-tocopherol was no longer decreased compared to baseline levels (29.6+/-7.4 mumol/l). MDA concentrations at baseline were significantly higher in the diabetic patients (3.79+/-2.91 mumol/l) than in the nondiabetic subjects (1.57+/-0.21 mumol/l, p=0.006). MDA concentrations decreased significantly following the start of insulin treatment. CONCLUSIONS: Patients with new-onset, insulin-dependent diabetes mellitus have alpha-tocopherol levels that are similar to those in normal subjects. Insulin treatment and/or improved metabolic control cause a significant decrease in alpha-tocopherol levels during the first months.

[From gene to disease; mutations in the WFS1-gene as the cause of juvenile type I diabetes mellitus with optic atrophy (Wolfram syndrome)]. / Van gen naar ziekte; mutaties in het WFS1-gen als oorzaak van juveniele type-1-diabetes mellitus met opticusatrofie (Wolfram-syndroom).

Wolfram syndrome patients are mainly characterised by juvenile onset diabetes mellitus and optic atrophy. A synonym is the acronym DIDMOAD: diabetes insipidus, diabetes mellitus, optic atrophy, deafness. Diabetes insipidus and sensorineural high-frequency hearing impairment are important additional features. This rare autosomal recessively inherited neurodegenerative syndrome is caused by mainly inactivating mutations in the WFS1 gene. It is located at chromosome 4p16 and encodes wolframin, a transmembrane protein. No function has yet been ascribed to this protein.

Clinical characteristics and outcome of patients with acute myocardial infarction and preinfarction angina.

OBJECTIVES/BACKGROUND: Preinfarction angina is associated with reduced myocardial infarct size in patients treated with thrombolysis. Our objective was to assess the relation between preinfarction angina and infarct size, left ventricular function and clinical outcome in patients treated with primary angioplasty (PTCA) and compare this with patients treated with thrombolysis. METHODS: In the Zwolle Infarction Study, 953 patients were treated for acute myocardial infarction between 1990 and 1996; 761 patients underwent primary PTCA and 192 patients received thrombolysis as reperfusion therapy. RESULTS: Preinfarction angina was present in about 50% of the patients, who were categorised into angina ≤24 hours and angina >24 hours before infarction. Patients in both treatment groups have a longer ischaemic time when preinfarction angina is present. In patients treated with thrombolysis, preinfarction angina ≤24 hours results in a smaller enzymatic infarct. Thrombolysis seems to be more effective when preinfarction angina occurs within the 24 hours prior to myocardial infarction. Collateral filling of the infarct-related artery is more often seen in patients with preinfarction angina. In the primary PTCA group, a longer ischaemic time in patients with preinfarction angina does not result in increased infarct size, and this effect remains after excluding patients with collateral filling. CONCLUSIONS: The protective effect of preinfarction angina is likely to be due to better collateral filling of the infarct-related artery and to ischaemic preconditioning of the myocardium.

Optimization of a classical aromatase activity assay and application in normal, adenomatous and malignant breast parenchyma.

The tritium water release assay, originally described for the analysis of aromatase activity in placental tissue, was used to estimate aromatase activity in breast tissue samples. The lower activity in this tissue necessitates longer incubation times and thus optimization of the assay conditions. To prevent oxidative and proteolytic inactivation of aromatase, dithiothreitol and albumin were added to the incubation mixture. Extra NADPH, cofactor in the aromatase reaction, also improved reaction rate in placental incubations, but after approximately 120 min activity rapidly decreased. Inhibitors gradually produced during the incubation could explain this phenomenon. Quantitative gas chromatography-mass spectrometry (GC-MS) analyses of testosterone, oestradiol, oestrone and androstenedione after incubation with non-labelled androstenedione proved that a substantial amount of the substrate is converted into testosterone. Qualitative GC-MS steroid profiling of the incubation mixture demonstrated the presence of hydroxylated oestradiol and hydroxylated testosterone, produced during incubation, which could have caused partial aromatase inhibition. The adjusted assay was used to analyse 84 breast tissue samples, histologically classified as normal, adenoma or carcinoma. Aromatase activity was found in 56% of all samples and ranged from 0.6 to 26 pmol oestrogen/g protein per hour. Aromatase positivity was found in 80% of the normal samples, 56% of the adenoma samples and 48% of the carcinoma samples. Although carcinoma samples were less often aromatase positive than normal tissue samples (chi2 = 4.80; P < 0.050) there was no difference in absolute aromatase activity. Because no less than approximately 50% of the carcinomas contained aromatase activity and because of the non-routine character of the assay we conclude that it is justified to start aromatase inhibition therapy without previous knowledge of the aromatase status.

Pharmacodynamic effects of depot-medroxyprogesterone acetate (DMPA) administered to lactating women on their male infants.

Normal postpartum women, who had a spontaneous vaginal delivery of one full-term male infant, free of congenital abnormalities and other diseases, were recruited for this study. Thirteen women received 150 mg depot-medroxy-progesterone acetate (DMPA), intramuscularly on days 42 + 1 and 126 + 1 postpartum. Infants of nine mothers, who did not receive DMPA, served as controls. Blood samples were collected from treated mothers on days 44, 47, 74, 124, 128, and 130 postpartum for medroxyprogesterone acetate (MPA) measurements. Four-hour urine collections were obtained from all 22 infants in the morning on days 38, 40, 42, 44, 46, 53, 60, 67, 74, 88, 102, 116, 122, 124, 126, 128, 130, and 137. Urinary follicle stimulating hormone (FSH), luteinizing hormone (LH), unconjugated testosterone, and unconjugated cortisol were measured by radioimmunoassay, and serum MPA and urinary MPA metabolites were measured by gas chromatography-mass spectrometry (GC-MS). No MPA metabolites could be detected in the urine of the infants from the DMPA-receiving mothers. Hormonal profiles in the urine samples were not suppressed in comparison with those of the control infants. The present study demonstrates that DMPA, administered to the mother, does not influence the hormonal regulation of the breast-fed normal male infant.