Infants born to women with substance use: Exploring early neurobehavior with the Dubowitz neurological examination.

BACKGROUND: There is a special concern regarding substance using pregnant women due to the possible adverse effects on the infant. While the immediate effects of prenatal substance exposure are well known, the long-term data on the infants' neurodevelopment is inconclusive. AIMS: The purpose of this study was to assess early neurobehavior of infants of mothers with substance use using the Dubowitz examination and to follow their neuromotor development until one year of age. STUDY DESIGN AND SUBJECTS: Ninety-five pregnant women with a recent history of substance use were recruited and followed up at the maternity outpatient clinic. Follow-up data was collected from hospital records and maternal interviews. The Dubowitz neurological examination was performed to the 54 clinically healthy term infants. The results were converted into optimality scores and compared to normative values from clinically healthy term infants derived from a separate normative population. The infant's neuromotor development was followed up to one year of age. RESULTS: Only 7% of the infants born to women with recent or current substance use reached optimal scores (<30.5) in the Dubowitz neurological examination compared to 95% reported in normative population. Sixty-three percent of the newborns needed follow-up based on physiotherapeutic assessment of neurobehavior. By 12 months of age, the neuromotor status of 88% (n = 30) of these infants was found normal. CONCLUSIONS: A high percentage of infants of mothers who were referred prenatally to hospital due to substance use showed suboptimal neurological findings during their first days of life.

Alterations in bile acid synthesis in carriers of hepatocyte nuclear factor 1α mutations.

OBJECTIVES: Heterozygous mutations in hepatocyte nuclear factor 1α (HNF1α) cause maturity onset diabetes of the young 3 (MODY3), an autosomal dominant form of diabetes. Deficiency of HNF1α in mice results in diabetes, hypercholesterolaemia and increased bile acid (BA) and cholesterol synthesis. Little is known about alterations in lipid metabolism in patients with MODY3. The aim of this study was to investigate whether patients with MODY3 have altered cholesterol and BA synthesis and intestinal cholesterol absorption. A secondary aim was to investigate the effects of HNF1α mutations on the transcriptional regulation of BA metabolism. METHODS: Plasma biomarkers of BA and cholesterol synthesis and intestinal cholesterol absorption were measured in patients with MODY3 (n = 19) and in matched healthy control subjects (n = 15). Cotransfection experiments were performed with several promoters involved in BA metabolism along with expression vectors carrying the mutations found in these patients. RESULTS: Plasma analysis showed higher levels of BA synthesis in patients with MODY3. No differences were observed in cholesterol synthesis or intestinal cholesterol absorption. Cotransfection experiments showed that one of the mutations (P379A) increased the induction of the cholesterol 7α-hydroxylase promoter compared with HNF1α, without further differences in other studied promoters. By contrast, the other four mutations (L107I, T260M, P291fsinsC and R131Q) reduced the induction of the farnesoid X receptor (FXR) promoter, which was followed by reduced repression of the small heterodimer partner promoter. In addition, these mutations also reduced the induction of the apical sodium-dependent bile salt transporter promoter. CONCLUSIONS: BA synthesis is increased in patients with MODY3 compared with control subjects. Mutations in HNF1α affect promoters involved in BA metabolism.

Impaired vibrotactile sense at low frequencies in fingers in autoantibody positive and negative diabetes.

Vibration thresholds in index and little finger pulps in subjects with autoantibody [GADA, IA-2A and/or ICA] positive and negative diabetes 20 years after diagnosis were higher than in age-matched controls at low frequencies (8 and 16 Hz), irrespective of HbA1c values, indicating selective impairment of Meissner's corpuscles and/or their innervating axons.

Characterization of beta cell and incretin function in patients with MODY1 (HNF4A MODY) and MODY3 (HNF1A MODY) in a Swedish patient collection.

The aim of this study was to evaluate the beta cell and incretin function in patients with HNF4A and HNF1A MODY during a test meal. Clinical characteristics and biochemical data (glucose, proinsulin, insulin, C-peptide, GLP-1 and GIP) during a test meal were compared between MODY patients from eight different families. BMI-matched T2D and healthy subjects were used as two separate control groups. The early phase of insulin secretion was attenuated in HNF4A, HNF1A MODY and T2D (AUC0-30 controls: 558.2 ± 101.2, HNF4A MODY: 93.8 ± 57.0, HNF1A MODY: 170.2 ± 64.5, T2D: 211.2 ± 65.3, P < 0.01). Markedly reduced levels of proinsulin were found in HNF4A MODY compared to T2D and that tended to be so also in HNF1A MODY (HNF4A MODY: 3.7 ± 1.2, HNF1A MODY: 8.3 ± 3.8 vs. T2D: 26.6 ± 14.3). Patients with HNF4A MODY had similar total GLP-1 and GIP responses as controls (GLP-1 AUC: (control: 823.9 ± 703.8, T2D: 556.4 ± 698.2, HNF4A MODY: 1,257.0 ± 999.3, HNF1A MODY: 697.1 ± 818.4) but with a different secretion pattern. The AUC insulin during the test meal was strongly correlated with the GIP secretion (Correlation coefficient 1.0, P < 0.001). No such correlation was seen for insulin and GLP-1. Patients with HNF4A and HNF1A MODY showed an attenuated early phase of insulin secretion similar to T2Ds. AUC insulin during the test meal was strongly correlated with GIP secretion, whereas no such correlation was seen for insulin and GLP-1. Thus, GIP may be a more important factor for insulin secretion than GLP-1 in MODY patients.

No signs of progressive beta cell damage during 20 years of prospective follow-up of autoantibody-negative diabetes.

Both type 1 and type 2 diabetes are considered to be associated with different degrees of progressive beta cell damage. However, few long-term studies have been made. Our aim was to study the clinical course of 20 years of diabetes disease, including diabetes progression, comorbidity, and mortality in a prospectively studied cohort of consecutively diagnosed diabetic patients. Among all 233 patients diagnosed with diabetes during 1985-1987 in Malmö, Sweden, 50 of 118 surviving patients were followed-up after 20 years. The age at diagnose was 42.3 ± 23.1 and 57.5 ± 13.6 years for antibody-positive and antibody-negative patients, respectively. HbA1c and plasma lipids were analyzed with regard to metabolic control. Islet antibody-negative patients at diagnosis had highly preserved C-peptide levels after 20 years in contrast to antibody-positive patients (antibody negative: C-peptide 0 years 0.78 ± 0.47 and 20 years 0.70 ± 0.46 (nmol/l), P = 0.51 and antibody positive: C-peptide 0 years 0.33 ± 0.35 and 20 years 0.10 ± 0.18; P < 0.001. Islet antibodies but not age, BMI, or C-peptide at diagnosis were predictors of C-peptide levels at 20 years when analyzed by logistic regression (P < 0.05). HbA1c did not differ between the groups after 20 years. The 20-year mortality was higher among antibody-negative patients, dependent on the higher age at diagnosis in this group (number of deaths: antibody positive: 18 of 56 vs. antibody negative: 109 of 188, P < 0.001). Of the deceased, 79% had died from diseases or complications that may be associated with diabetes. We found no progressive beta cell damage in autoantibody-negative diabetes at a 20-year follow-up of the clinical course of diabetes.

Abnormal antenatal Doppler velocimetry and cognitive outcome in very-low-birth-weight infants at 2 years of age.

OBJECTIVE: To study neurodevelopmental outcome at 2 years of corrected age in very-low-birth-weight (VLBW) (< or = 1500 g) preterm infants with abnormal fetoplacental flow. METHODS: A total of 258 VLBW infants were born at Turku University Hospital between 2001 and 2006. Of these, 99 had undergone, within 1 week of delivery, antenatal Doppler assessment of blood flow in the umbilical artery (UA), fetal middle cerebral artery (MCA), descending aorta (DAo), aortic isthmus and ductus venosus and were eligible for inclusion in the study. Postnatally brain pathology was assessed by serial ultrasound and magnetic resonance imaging in 86 of the neonates and brain volume was measured in 80. Cognitive development was evaluated at 2 years of corrected age in 83 infants using the Bayley Scales of Infant Development-II. Motor development was assessed using the Hammersmith Infant Neurological Examination. RESULTS: On univariate analysis, abnormal pulsatility index (PI) in the UA and an abnormal UA-PI/MCA-PI ratio (P = 0.04 and P = 0.003, respectively) as well as increases in both the DAo-PI and in the DAo-PI/MCA-PI ratio (P = 0.03 and P = 0.02, respectively), were associated with adverse cognitive outcome at 2 years of age. However, when controlling for cerebral volume using multivariate analysis, the association between abnormal antenatal Doppler characteristics and cognitive outcome became statistically non-significant, which indicated the determinant role of the volume reduction. Motor development was not associated with antenatal Doppler indices. CONCLUSION: Abnormal antenatal Doppler indices are associated with adverse cognitive outcome at 2 years in VLBW infants. Our findings suggest that this association may be mediated through brain volume.

Change in heart rate variability in relation to a significant ST-event associates with newborn metabolic acidosis.

OBJECTIVE: To find whether low-to-high frequency (LF/HF) ratio of fetal heart rate (FHR) variability changes in relation to a significant ST-event during delivery, and if the change is predictive of metabolic acidosis of the newborn. DESIGN: A case-control study. SETTING: Data from a multicentre project. SUBJECTS: Acidotic and control fetuses with abnormal cardiotocography together with a ST-event in fetal electrocardiogram (ECG). METHODS: We studied intrapartum FHR variability with spectral analysis from 34 fetuses with a significant ST-event in the fetal ECG. LF/HF ratio of FHR variability was measured within a period of 1 hour before and 1 hour after a significant ST-event. Sensitivity and specificity of the change in LF/HF ratio of FHR variability in prediction of metabolic acidosis (pH < or = 7.05 and base deficit value > 12.0 mmol/l) of the newborn were described by means of the receiver operating characteristic curve. MAIN OUTCOME MEASURES: Change in LF/HF ratio of FHR in relation to a significant ST-event. RESULTS: We found that a relative change in LF/HF ratio greater than 30% in relation to a significant ST-event predicted cord arterial metabolic acidosis with a sensitivity of 89% (95% CI 68-100%) and specificity of 80% (95% CI 64-96%). CONCLUSIONS: Relative changes in LF/HF ratio of FHR variability in relation to a significant ST-event are more pronounced in fetuses born with metabolic acidosis.

Immediate effects of docetaxel alone or in combination with epirubicin on cardiac function in advanced breast cancer.

The immediate effects on cardiac function of 3-weekly docetaxel and combined docetaxel-epirubicin were evaluated during treatment of metastatic breast cancer using assessment of heart rate variability (HVR) and left ventricular ejection fraction (LVEF) measured by echocardiography. Twenty-four breast cancer patients were treated with docetaxel alone (starting dose 100 mg/m2) and 34 with a combination of docetaxel and epirubicin (starting dose for both drugs 75 mg/m2) administered 3-weekly. Single docetaxel caused no significant changes in HVR or cardiac function, whereas during combined treatment statistically significant changes were observed in mean RR intervals and in the number of supraventricular extrasystoles. Clinically the observed changes were insignificant. In conclusion, in 3-weekly administration the combined use of docetaxel and epirubicin was more likely than single docetaxel to cause changes in cardiac function.

Docetaxel with epirubicin--investigations on cardiac safety.

The aim was to evaluate clinical and subclinical cardiac toxicity of epirubicin-docetaxel (ET) combination. Breast cancer patients were given epirubicin (75 mg/m2 for 15 min), followed 1 h later by a 1-h infusion of docetaxel (75 mg/m2) q3w as first-line treatment. Cardiac function was monitored using a 24-h ambulatory electrocardiogram (ECG), left ventricular ejection fraction (LVEF), physical examination and chest radiography. The median LVEF did not decrease during the course of the treatment: median LVEF was 64% prior to treatment and 68% after cycle 8. The 24-h ECG did not reveal any significant changes in heart rate variability. The number of extrasystoles or cardiac arrhythmia did not increase with the ET treatment. No patient experienced congestive heart failure during treatment or the mean follow-up of 34 months. We conclude that first-line ET caused no major cardiac changes during 6 months of treatment (8 cycles) or during follow-up. Twenty-four-hour ECG, combined with echocardiography to measure LVEF, was a feasible method for the close monitoring of the cardiac effects during chemotherapy.

Epirubicin/docetaxel regimen in progressive breast cancer-a phase II study.

The purpose of this investigation was to evaluate the efficacy and toxicity of 6 months' treatment with the combination of epirubicin and docetaxel in metastatic breast cancer. Thirty-eight women (mean age 51 years, range 35-72) with metastatic breast cancer were treated with a regimen of epirubicin 75 mg/m and docetaxel 75 mg/m every 3 weeks, given 4 times if progression was seen upon evaluation after 4 courses or 8 times in responding/stable patients. The patients received 285 cycles of combination treatment and two treatments with docetaxel or epirubicin alone. When neutropenia with fever was observed, further cycles were given with dose reduction. The median cumulative docetaxel dose was 462 mg/m (range 199-600) and that of epirubicin 476 mg/m (range 199-740). The overall response rate was 54% (95% CI 37-71), with a median duration of response of 14.8 months (95% CI 8.8-27.8). Median time to progression was 12 months, median survival 26 months. Neutropenia below 0.5 x 10 /l occurred following 113 (39%) of the total of 285 cycles given; 21 patients (55%) were hospitalized for febrile neutropenia. We conclude that dose tailoring is required in treatment with an epirubicin and docetaxel regimen to avoid grade 3/4 adverse effects in a significant number of patients treated for metastatic breast cancer.

Comparison of ovarian cyst formation in women using the levonorgestrel-releasing intrauterine system vs. hysterectomy.

OBJECTIVE: To analyze the effect of the levonorgestrel-releasing intrauterine system (LNG-IUS) on ovarian cyst formation, endometrial thickness and the size of uterus and uterine fibroids by ultrasonography. SUBJECTS AND METHODS: This was a prospective, randomized trial comparing the LNG-IUS and hysterectomy in 236 women (age range 35-49 years) referred for menorrhagia. Transvaginal ultrasound examination was used to study the presence of ovarian cysts, uterine size, endometrial thickness, and the size of the uterus and uterine fibroids during a 12-month follow-up period. RESULTS: At baseline examination, 12 ovarian cysts were detected, eight in the LNG-IUS group and four in the hysterectomy group. During the follow-up period, 14 new cysts had emerged at 6 months and 14 new cysts had emerged at 12 months in the LNG-IUS group, whereas the corresponding figures in the hysterectomy group were three and eight, respectively. All but one of the 14 new cysts (94.1%) detected at 6 months in the LNG-IUS group resolved spontaneously, whereas two out of the eight cysts detected at the baseline examination persisted for 12 months. Three cysts were removed at operation. The relative risk of the occurrence of ovarian cysts was significantly higher in women with LNG-IUS, compared with women who underwent hysterectomy. LNG-IUS did not affect the size of the uterus or uterine fibroids, but it was associated with a decrease in endometrial thickness. The occurrence of cysts did not correlate with age or follicle stimulating hormone levels, but a weak positive correlation between the occurrence of cysts and the presence of irregular bleeding was observed. CONCLUSIONS: LNG-IUS use in the treatment of menorrhagia was associated with the development of ovarian cysts, but these were symptomless and showed a high rate of spontaneous resolution. LNG-IUS did not affect the size of the uterus or the size of uterine fibroids, but decreased the thickness of the endometrium.

Periodic spectral components of fetal heart rate variability reflect the changes in cord arterial base deficit values: a preliminary report.

Fetal distress changes the function of the autonomic nervous system. These changes are reflected in the fetal heart rate and can be quantified with power spectrum analysis of heart rate variability. The purpose of this study was to find out whether spectral components of fetal heart rate variability (FHRV) during labor are associated with fetal cord arterial base deficit values at birth. The association between FHRV and umbilical cord arterial base deficit was studied in 14 singleton fetuses with normal pregnancy at 35-40 weeks of gestation. Fetal ECG was recorded by scalp-electrode using a STAN Fetal ECG monitor (Cinventa Ab, Mölndal, Sweden). FHRV was quantified by computing Fast-Fourier-transformed heart rate (HR) spectra at three frequency bands: low-frequency (LF) 0.03-0.07 Hz, mid-frequency (MF) 0.07-0.13 Hz and high-frequency (HF) 0.13-1.0 Hz. We found that total FHRV and MF FHRV were lower in fetuses with cord arterial base deficit 8 to 12 mmol/L in comparison to the fetuses with normal cord arterial base deficit value (P=0.02 and P=0.01, respectively). A linear correlation was found between the spectral densities and the cord arterial base deficit values (r=0.4 and r=0.6, respectively). We conclude that the results suggest changes in the autonomic nervous cardiac control in fetuses with cord arterial base deficit between 8 to 12 mmol/L. The clinical applicability of our observations on FHRV in predicting fetal distress remains to be further studied.

The effect of estrogen replacement therapy on cardiac autonomic regulation.

OBJECTIVE: To study the effects of estrogen replacement therapy (ERT) and sleep stage on autonomic cardiac regulation. SRUDY DESIGN: Seventy-one healthy postmenopausal women received transdermal ERT and placebo separated by a washout in a randomized, placebo-controlled, double-blind, cross-over trial. Polysomnography was conducted at the end of each treatment. Heart rate variability (HRV) was assessed in epochs of the awake state, stage 2, slow wave and REM sleep. The effects of estradiol and sleep stages on HRV were analyzed. RESULTS: ERT decreased heart rate in the awake state and quiet sleep, but not in REM sleep. ERT did not change the heart rate variability. Heart rate decreased and HRV increased during stage 2 and slow wave sleep compared with the awake state with placebo. In REM sleep, similarly, heart rate increased above awake values and the values of HRV parameters fell back to awake levels. CONCLUSIONS: The results suggest that ERT increases vagal tone, but does not change cardiac vagal modulation. Changes in HRV suggest a strong vagal influence in non-REM and a sympathetic influence in REM sleep.

Placental expression of syndecan 1 is diminished in preeclampsia.

OBJECTIVE: Syndecan 1 is a cell surface heparan sulfate proteoglycan that binds growth factors and antithrombin III. The objective of this study was to examine whether placental expression of syndecan 1 in preeclampsia differs from that in normal pregnancy and whether gestational age and fetal growth affect syndecan 1 expression. STUDY DESIGN: An immunohistochemical analysis of 30 placentas of women with severe preeclampsia and 15 placentas of women without preeclampsia was performed with the monoclonal anti-syndecan 1 antibody B-B4. RESULTS: In 47% of preeclamptic placentas the immunoreactivity with antibody B-B4 was faint or absent, whereas 93% of the normal placentas exhibited strong immunoreactivity. The reduction in placental expression of syndecan 1 in preeclampsia was not associated with gestational age or impaired fetal growth. CONCLUSION: The expression of syndecan 1 on the chorionic villi is reduced in preeclampsia irrespective of gestational age or fetal growth.

Expression of extracellular matrix genes: transforming growth factor (TGF)-beta1 and ras in tibial fracture healing of lathyritic rats.

Experimental osteolathyrism, induced by dietary aminoacetonitrile (AAN), was used to study the effect of altered extracellular matrix on the expression of connective tissue components in long bone healing. AAN inhibits lysyl oxidase, which is needed for the formation of collagen cross-link precursors, and is also shown to act as a regulator of Ras. Fractured tibias in lathyritic rats develop excessive amounts of mechanically weak callus tissue with irregular cartilage and reduced glycosaminoglycan accumulation. Cartilage-specific proteins (collagen types II, IX, and X and aggrecan) were expressed temporally much wider in lathyritic calluses than in the controls, and active transcription was observed even during the fibrous and ossifying stages. Soft connective tissue was still present in 2- and 3-week-old lathyritic calluses and could explain the elevated type III collagen, biglycan, and decorin mRNA levels. Both transforming growth factor (TGF)-beta1 and c-Ha-ras, which control cell growth and differentiation, were upregulated during the cartilaginous stage. The maximal expression of TGF-beta1 preceded that of ras in osteolathyrism.

Docetaxel and autonomic cardiovascular control in anthracycline treated breast cancer patients.

BACKGROUND: Taxoids are new chemotherapeutic agents effective in the treatment of breast cancer. Paclitaxel treatment has been reported to cause some cardiac side effects and both paclitaxel and docetaxel to cause mild, mainly sensory, peripheral neuropathy. Autonomic function tests are sensitive measures of autonomic neuropathy and cardiac regulation. The purpose of this study was to find out whether docetaxel changes neural cardiovascular regulation in breast cancer patients previously treated with anthracyclines. PATIENTS AND METHODS: Nine women treated for metastatic breast cancer with docetaxel were studied prior to the docetaxel treatment and after the third or fourth course. Autonomic cardiovascular function tests were performed and heart rate and blood pressure variability were assessed with power spectrum analysis. RESULTS: Heart rate variability or the heart rate responses to the autonomic function tests did not change after docetaxel treatment. The blood pressure response to standing was enhanced and systolic blood pressure variability decreased after three to four cycles of docetaxel. CONCLUSIONS: Docetaxel treatment did not deteriorate vagal cardiac control in breast cancer patients after exposure to epirubicin. The observed changes in blood pressure responses suggest that docetaxel changes sympathetic vascular control. However, these changes seem to be related to altered cardiovascular homeostasis rather than peripheral sympathetic neuropathy.

Impairment of heart rate variability during paclitaxel therapy.

BACKGROUND: Paclitaxel, which has been reported to be effective in treating metastatic breast carcinoma and advanced ovarian carcinoma, has been associated with cardiac side effects. Therefore, the effect of paclitaxel on cardiovascular autonomic regulation was studied. METHODS: Twenty-four-hour ambulatory electrocardiogram measurements were recorded twice from 14 women with breast or ovarian carcinoma: once before paclitaxel treatment and once on the day after the second chemotherapy course. Heart rate variability (HRV) was assessed with spectral analysis. For the frequency domain analysis, HRV was assessed in the very low (0.005-0.040 hertz [Hz]), low (0.040-0.150 Hz), and high frequency (0.150-0.400 Hz) spectral components. RESULTS: The ratio between low frequency and high frequency HRV decreased (daytime values of 2.7% [standard deviation (SD) 1.6] vs. 1.7% [SD 0.91; P = 0.0098) after 2 courses of paclitaxel. The circadian fluctuation of HRV also decreased in all studied frequency components. CONCLUSIONS: The observed changes in spectral characteristics suggest that autonomic modulation of the heart rate is impaired after paclitaxel therapy. However, from these data it is not clear whether the observed changes are permanent or whether autonomic cardiac function returns to normal some time after treatment. Further studies are needed to examine whether these indices based on HRV can be used to detect those patients at risk for cardiac side effects during chemotherapy.

Pre-eclampsia does not change the adhesion molecule status in the placental bed.

During normal placentation trophoblast cells invade maternal tissues and remodel the uterine arteries into low-resistance channels. In pre-eclampsia, trophoblast invasion is impaired and this, along with endothelial dysfunction, has been suggested to play a role in the pathogenesis of pre-eclampsia. We studied the expression of adhesion molecules important for leukocyte extravasation in the placental bed with immunohistochemistry and compared the expression in pre-eclampsia to that in normal pregnancy. Our major finding was that only invasive trophoblasts expressed cutaneous lymphocyte antigen-1 (CLA-1) in the third trimester of pregnancy, whereas villous trophoblasts did not. In the first trimester both villous trophoblasts and invasive trophoblast cells in decidua remained negative for CLA-1. Pre-eclampsia did not change the expression of leukocyte-endothelium adhesion or lymphocyte homing-associated antigens, ICAM-1, ICAM-2, VCAM, P-selectin, E-selectin, L-selectin, CLA-1, CD73, VAP-1 and alphaEbeta7 in the placental bed. Furthermore, pre-eclampsia was not associated with an aberrant accumulation of lymphocytes carrying antigens of any particular known organ-specific homing systems. The results on the unchanged pattern of adhesion molecule expression in pre-eclampsia suggests that there is no major change in the adhesive properties of the endothelium of the placental bed in pre-eclampsia.

Expression of stratum corneum chymotryptic enzyme in relation to other markers of epidermal differentiation in a skin explant model.

The serine proteinase stratum corneum chymotryptic enzyme (SCCE) has been proposed to be involved in the degradation of intercellular cohesive structures in cornified squamous epithelia in the process of desquamation. Since SCCE is expressed late in epidermal differentiation and is found at all sites where there is a formation of cornified epithelia it also serves as a marker for terminal epidermal differentiation. Earlier studies have shown that the link between expression and the formation of cornified cells may be stronger for SCCE than for other well characterized markers of epidermal differentiation. In an attempt to further elucidate the regulation of SCCE expression we have in this study compared the expression of SCCE with the expression of keratin 10, filaggrin and involucrin in an in vitro model with skin explants cultured for various periods of time on de-epidermized dermis at the liquid-air interface. The markers were analysed by means of immunohistochemistry. We found that the expression of SCCE preceded the expression of keratin 10 and filaggrin. In contrast to involucrin, which was expressed by all suprabasal keratinocytes, SCCE was expressed only by high suprabasal cells. Our results indicate that the expression of SCCE may be regulated in a way that differs from the regulation of the expression of keratin 10, filaggrin and involucrin.

Docetaxel, a promising novel chemotherapeutic agent in advanced breast cancer.

UNLABELLED: Clinical practice in chemotherapy of breast cancer is undergoing changes. This study investigated the efficacy and toxicity of docetaxel, a novel chemotherapeutic agent in metastatic breast cancer. Focus was on the effect of the cumulative dose of previous anthracycline treatment on response rate, toxicity and survival in our own patients; published data were reviewed. PATIENTS AND METHODS: Thirty-one women, (median age 52 years, range 40-65) treated for metastatic breast cancer with docetaxel were included. RESULTS: The overall response rate was 48%, with 3 complete and 11 partial responses (95% CI 29-66). The duration of response was 7 months (range 2 to 16 months), the median overall survival after docetaxel 13.7 months for responding patients, 14.3 months in no-change patients and 6.5 months in patients with progressive disease. The mean cumulative anthracycline dose prior to docetaxel was 860 mg (range 200-1760 mg); in the case of responders, the previous cumulative total epirubicin doses were 200-1575 mg (median 766 mg.). Total dose or schedule of previous epirubicin treatment had no impact on docetaxel response rate, toxicity or survival. The response seen in this study is within the published range (24 to 60%) observed for docetaxel in anthracycline-treated patients. CONCLUSION: We conclude that docetaxel is active in metastatic breast cancer even as third- line treatment. Previous treatment with, or response to, epirubicin does not influence the response to docetaxel and this promising new drug is currently being tested for adjuvant use in breast cancer.