Transfer of metformin into human milk.
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Adult↗
Biomedical subjects
J Kristensen
Publications and source records attributed to J Kristensen.
Pseudoephedrine effects on milk production in women and estimation of infant exposure via human milk.
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Adrenergic alpha-Agonists↗
Convergent synthesis of 3-arylated 1-hydroxypyrazoles via 3-metalated pyrazole-1-oxides.
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Acetylation↗
Synthesis of ortho substituted arylboronic esters by in situ trapping of unstable lithio intermediates.
[reaction: see text] Ortho lithiation-in situ boration using lithium 2,2,6,6-tetramethylpiperidide (LTMP) in combination with triisopropylborate (B(OiPr)(3)) is a highly efficient and experimentally straightforward process for the preparation of ortho substituted arylboronic esters. The mild reaction conditions allow the presence of functionalities such as ester or cyano groups or halogen substituents that are usually not compatible with the conditions used in directed ortho metalation of arenes. The arylboronic esters underwent Suzuki-type cross-coupling with a range of aryl halides, furnishing biaryls in 53-94% yield.
Journal Article↗
In vivo activity of CHS 828 on hollow-fibre cultures of primary human tumour cells from patients.
Fresh human tumour cells from patients with ovarian cancer and chronic lymphocytic leukaemia were cultured in semipermeable hollow fibres. The fibres were implanted on immunocompetent rats, which were treated with the cyanoguanidine N-(4-chlorophenoxyhexyl)-N'-cyano-N"-4-pyridylguanidine (CHS 828). CHS 828 showed high antitumour activity against all eight tumour samples; the fibres from control animals had a mean net growth of 73% while CHS 828 treatment induced a 37% mean reduction of cell density, without observable haematological toxicity. The results show a feasibility of using tumour cells directly from patients in the hollow-fibre rat model.
Aged↗
Temporal effects of the novel antitumour pyridyl cyanoguanidine (CHS 828) on human lymphoma cells.
CHS 828, a novel pyridyl cyanoguanidine, has shown potent antitumour activity both in vitro and in vivo and is currently undergoing phase I evaluation in humans in collaboration with the European Organization for Research and Treatment of Cancer (EORTC). Here we study the temporal effects of CHS 828 on cytotoxicity, protein and DNA synthesis, cellular morphology and ultra structure using the lymphoma cell line U-937 GTB as the primary tumour model. In vitro analysis of tumour cell survival in response to CHS 828 revealed a cytotoxic effect progressively increased as a function of exposure time with maximum efficacy observed after 72 h. Activity of CHS 828 on U-937 GTB cells grown in vivo was also found. CHS 828 induced-cell death was dependent on intact protein synthesis and most cells appeared to lose their membrane integrity in the presence of a relatively well preserved nuclear structure. The results indicate that CHS 828 induced active and delayed cell death with a non-apoptotic morphology.
Antineoplastic Agents↗
Activity of CHS 828 in primary cultures of human hematological and solid tumors in vitro.
CHS 828 is a pyridyl cyanoguanidine that has shown promising preclinical anticancer activity against various experimental tumor models and is presently being tested in a phase II trial in man. In the present study the fluorometric microculture cytotoxicity assay was used for in vitro evaluation of CHS 828 activity in primary cell cultures from hematological and solid tumors. In total, 156 samples from various diagnoses were tested with 72-h continuous drug exposure. CHS 828 showed high relative in vitro activity against tumor cells from chronic lymphocytic leukemia as well as from acute leukemia and high-grade lymphoma. Activity was also observed in several solid tumor cell samples, although the group as a whole appeared less responsive. CHS 828 was significantly more active against hematological malignancies compared to normal lymphocytes. Correlation analysis with standard drugs revealed low to moderate correlation coefficients. The results show that CHS 828 has potent antitumor activity against primary cultures of human tumor cells from patients and might have a unique mechanism of action.
Adolescent↗
Direct pelletization in a rotary processor controlled by torque measurements. I. Influence of process variables.
The aim of this study was to elucidate the feasibility of using torque measurement to control the end point of a wet pelletization process in a rotary processor at varying levels of friction plate rotation speed, air gap pressure difference, and batch size. A 1:1 mixture of lactose monohydrate (200 mesh) and microcrystalline cellulose (PH-101) was granulated into pellets in an instrumented laboratory scale rotary processor using water as aqueous binder liquid. A full factorial designed study was performed to investigate the influence of the friction plate rotation speed (600 and 1200 rpm), the air gap pressure difference (1 and 3 kPa), the torque increase (0.4 and 0.8 N.m) and the batch size (500 and 1000 g) on the pellet properties. All pellets produced were round and showed a narrow size distribution. The geometric mean diameter varied from 400 to 1900 microns with a good reproducibility. Increasing the batch size and the rotation speed led to smaller pellets, whereas a higher torque produced larger pellets. This study showed that the process can be controlled by means of the torque increase because it was possible to produce pellets of a reproducible size by stopping the liquid addition at a certain torque level.
Drug Compounding↗
Direct pelletization in a rotary processor controlled by torque measurements. II: effects of changes in the content of microcrystalline cellulose.
In the present study we investigated the effect of changes in the content of microcrystalline cellulose (MCC) on a direct pelletization process in a rotary processor in which the liquid addition was terminated once a certain increase in torque was produced. Nine different mixtures of MCC and lactose with MCC contents varying from 10% to 100% (w/w) were pelletized using 6 different torque increase levels, and the changes in pellet characteristics were investigated. The pellet characteristics investigated were pellet shape, size, and size distribution as well as the water content of the pellets at the end of liquid addition. To produce spherical agglomerates with suitable characteristics in a reproducible way, a content of at least 20% (w/w) MCC was found necessary. Linear correlations were found between the MCC content and the water content and between the torque increase and the water content, showing that the torque increase is suitable to control the process. A higher torque increase or a higher MCC content was found to increase the water content independently of each other.
Cellulose↗
Evaluation of purine and pyrimidine analogues in human tumor cells from patients with low-grade lymphoproliferative disorders using the FMCA.
The purine analogues fludarabine and cladribine (CdA) have recently become established to be effective treatment for low-grade non-Hodgkin's lymphoma (NHL). The pyrimidine nucleoside analogue cytarabine (AraC) has an important place in the treatment of acute leukemia, and gemcitabine is a new pyrimidin antimetabolite which has shown clinical activity against solid tumors. We have used the semiautomated fluorometric microculture cytotoxicity assay (FMCA), based on the measurement of fluorescence generated from cellular hydrolysis of fluorescein diacetate (FDA), to study these drugs. Eighty samples from 60 patients with low-grade NHL were studied. Fifty samples from patients with acute lymphoid leukemia (ALL) and 118 samples from patients with acute myeloid leukemia (AML) were included for comparison. The results indicate that the purine- and pyrimidine nucleoside analogues tested may be as active against low-grade NHL as against acute leukemia. In low-grade NHL, AraC seems to be even more active in comparison to CdA (p=<0.0001) and fludarabine (p=0.001). Untreated patients were more drug sensitive than previously treated patients. Gemcitabine showed the highest correlation with AraC (0.90) whereas CdA showed the highest correlation with fludarabine (0.84). Based on these results we propose that AraC and gemcitabine may have a role in the treatment of low-grade NHL.
Acute Disease↗
[Significance of idiopathic preterm birth in relation to previous and future pregnancies].
This registry-based cohort study aimed to describe the relationship between pregnancy complications in the first and second pregnancy, focussing on idiopathic and indicated preterm birth of singleton infants in either pregnancy. The cohort consisted of all women living in Denmark with a first singleton birth in 1982 and a second in the period 1982-1987 (13,967 women). The risk of a second preterm birth was not significantly different between women who had an idiopathic or an indicated first preterm birth (15.2 and 12.8% respectively). Adjustment by logistic regression analysis for other risk factors for preterm birth did not influence the relative risk (6.0 before 32 weeks and 4.8 between 32 and 36 weeks) of a second preterm birth subsequent to a first one. Women with idiopathic preterm delivery in their first or second pregnancies give birth to infants with lower birth weight in previous or subsequent pregnancies. Emergency cesarean section in a first term pregnancy was a risk factor for subsequent idiopathic preterm birth.
Cesarean Section↗
Nonsteroidal antiinflammatory drugs during lactation.
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Anti-Inflammatory Agents, Non-Steroidal↗
Cytotoxic activity of cyclosporin A and [3-keto-Bmt1]-[Val2]-cyclosporin (SDZ PSC 833) on tumour cells from patients with haematological malignancies.
OBJECTIVE AND METHOD: The fluorometric microculture cytotoxic assay was employed for characterisation of the cytotoxic effect of cyclosporin A (CsA) and its non-immunosuppressive analogue SDZ PSC 833, [3-keto-Bmt1]-[Val2]-cyclosporin (PSC) in tumour cells from patients with haematological or solid tumours. RESULTS: Tumour cells from patients with chronic lymphocytic leukemia (CLL) or non-Hodgkin's lymphoma (NHL) were found to be more sensitive to both drugs than those of tumour cells from patients with acute lymphocytic leukemia (ALL), acute myoblastic leukaemia (AML) and various solid tumours. There was a close correlation between the effects of the two drugs (correlation coefficient 0.71), but CsA was slightly more active than PSC in most diagnoses. No tumour cells sample showed sensitivity to PSC without also being sensitive to CsA. There was a moderate level of correlation between the activity pattern of CsA and doxorubicin (correlation coefficient 0.66), whereas the correlations with other cytostatics, such as vincristine, cytarabine and melphalan, were low (correlation coefficient -0.11 to 0.33). CONCLUSION: The results indicate that PSC shares the direct cytotoxic properties of CsA, but is slightly less potent. Clinical testing of the cytotoxic effect of these agents in haematological malignancies seems warranted and the apparent non-cross-resistance with standard agents makes cyclosporins a potentially useful adjunct to chemotherapy in those diagnoses.
Antineoplastic Agents↗
Ampicillin-metronidazole treatment in idiopathic preterm labour: a randomised controlled multicentre trial.
OBJECTIVE: To determine whether treatment with ampicillin and metronidazole in women with threatened idiopathic preterm labour will prolong the gestation and reduce maternal and neonatal infectious morbidity. DESIGN: Randomised controlled double-blind trial. SETTING: Six obstetric departments in the Copenhagen area. POPULATION: One hundred and twelve women with singleton pregnancies, with threatened idiopathic preterm labour and intact amniotic membranes at 26 to 34 weeks of gestation. METHODS: Random allocation to eight days intravenous and oral treatment with ampicillin and metronidazole, or placebo. MAIN OUTCOME MEASURES: Number of days from admission to delivery, gestational age at delivery, rates of preterm delivery, low birthweight, maternal infections and neonatal infections. RESULTS: Treatment with ampicillin and metronidazole was associated with a significant prolongation of pregnancy (admission to delivery 47.5 days versus 27 days, P < 0.05), higher gestational age at delivery (37 weeks versus 34 weeks, P < 0.05), decreased incidence of preterm birth (42% versus 65%, P < 0.05), and lower rate of admission to neonatal intensive care unit (40% versus 63%, P < 0.05), when compared with placebo treatment. Antibiotic treatment had no significant effects on infectious morbidity. CONCLUSIONS: Treatment with ampicillin and metronidazole in women with threatened idiopathic preterm labour significantly prolonged the gestation, but had no effects on maternal and neonatal infectious morbidity.
Administration, Oral↗
[Idiopathic preterm deliveries in Denmark].
The objective of the study was to characterize and quantify various demographic factors in idiopathic preterm delivery. All women with a permanent address in Denmark with singleton pregnancies who gave birth to an infant in 1982 (n = 51,851) are included. The material was obtained by a linkage of the Medical Birth Register and the National Register of Hospital Discharges, using the personal identification number. The incidence of singleton preterm delivery was 4.5% (n = 2330) of which 67% (n = 1557) were idiopathic. Neonatal mortality rates were significantly lower in idiopathic compared to indicated preterm birth. Following stepwise logistic regression analysis, maternal age below 20 (adjusted odds ratio 1.63, 95% confidence interval (CI) 1.07-2.47; p < 0.03), maternal age above 30 (adjusted odds ratio 0.74, 95% CI 0.60-0.90; p < 0.004) and being married (adjusted odds ratio 0.63, 95% CI 0.43-0.94; p < 0.03) correlated with idiopathic preterm birth. It is concluded that idiopathic preterm birth is more common in single, young women and associated with lower neonatal mortality rate than indicated preterm birth.
Adult↗
Intrauterine growth and gestational age in preterm infants with cerebral palsy.
In a case-control study, gestational age and intrauterine growth of 191 preterm singleton infants 1971-82 with cerebral palsy were compared to all preterm live-born singletons in Denmark in 1982 (N = 2203). The distribution of gestational age among preterm cases was slightly bimodal with maximum values at 29 and 32 weeks. The risk for cerebral palsy was highest in the infants with gestational age 28-30 weeks (OR = 5.6 (4.0-7.8), 95% confidence interval). Birth weight deviation, in the 34-36 weeks infants, expressed as the number of standard deviations from the mean birth weight for gestational age, was more negative in cases than in controls (P < 0.001). The frequency of small for gestational age (SGA) was 13% in cases and 9% in controls (OR = 1.5 (0.96-2.3), 95% confidence interval). The odds for cerebral palsy being SGA, was lower in 28-30 weeks (OR = 0.22 (0.06-0.86), 95% confidence interval), the same in 31-33 weeks (OR = 0.83 (0.35-2.0), 95% confidence interval) and higher in 34-36 weeks (OR = 5.2 (2.9-9.5), 95% confidence interval). In conclusion, preterm infants with cerebral palsy are born earlier than other preterm infants. Small for gestational age is associated with cerebral palsy in preterm infants only above 33 weeks.
Case-Control Studies↗
Validation of the Danish Birth Registration.
We assessed validity and reliability of data on four serious pregnancy complications and gestational age in two national registers, the Medical Birth Register (MBR) and the National Register of Hospital Discharges (NRHD). From a cohort of all women in Denmark who gave birth to their first and second singleton infant in 1982-1987, a review was made of a selected sample of 1662 medical records. Regarding registration of pregnancy complications, there was good agreement (kappa above 0.6) between medical records and the registers, and between the registers. However, there was a tendency toward understatement evidenced by low sensitivity of three of four pregnancy complications. The level of agreement (43%) for length of gestation was disappointing. The number of systematic and nonsystematic errors indicate that there was about 52% more singleton preterm deliveries in Denmark in 1982 than previously reported (6.9% instead of 4.5%). It is concluded that the validity of the Danish birth registers should be improved by explicit definitions, increased use of raw data, and data collection by motivated professionals at birth.
Denmark↗
Evaluation of platelet function using the in vitro bleeding time and corrected count increment of transfused platelets. Comparison between platelet concentrates derived from pooled buffy coates and apheresis.
The functional capacity of transfused platelets was evaluated with in vitro bleeding time (IVBT) and corrected count increment (CCI) in order to compare platelet concentrates (PCs) derived from pooled buffy coats (BC-PCs) with PCs collected by apheresis (A-PCs). The suspension medium in the BC-PCs was 30% CPD plasma and 70% of an additive solution (containing sodium and potassium chloride, sodium citrate and phosphate, mannitol), and in the A-PCs the medium was 100% CPD plasma. IVBT was evaluated using a Thrombostat 4000/2. BC-PC and A-PC were transfused 57 and 41 times, respectively to 36 patients with chemotherapy-induced thrombocytopenia. PCs transfused within 2 days of donation were considered fresh, and those transfused within 3-5 days were considered stored. IVBT was determined before, as well as 10-30 min and 24 h after transfusion; CCI was determined 10-30 min and 24 h after transfusion. The median pretransfusion IVBT value was 486 s. It was measurable in 21 of 98 (21%) of the transfusions, i.e. below the cutoff limit of 486 s. Ten to 30 min after transfusion, the IVBT showed a measurable reduction in 90% of the transfusions with fresh BC-PCs, 92% of those with fresh a-PCs, 63% of those with stored BC-PCs and 79% of those with stored A-PCs. After 24 h, the corresponding values were 63% for fresh BC-PCs, 50% for fresh A-PCs, 26% for stored BC-PCs and 38% for stored A-PCs. The median value of CCI 10-30 min after transfusion was 20 for fresh BC-PCs, 17 for fresh A-PCs, 16 for stored BC-PCs and 14 for stored A-PCs. The difference in IVBT between fresh and stored BC-PCs was significant (p = 0.032), unlike that between fresh and stored A-PC. After 24 h the corresponding values were 7 for fresh BC-PCs, 4 for fresh A-PCs, 4 for stored BC-PCs and 3 for stored A-PCs. When all transfusions with fresh PCs (BC-PCs + A-PCs) were compared with all transfusions with stored PCs, a statistical difference was demonstrated in both CCI (p = 0.027) and IVBT (p = 0.043). Spearman's rank correlation coefficient (rs) was -0.41 between CCI and IVBT < 486 s 10-30 min after transfusion, and -0.55 between the posttransfusion platelet count and IVBT, indicating a relatively poor correlation between CCI and IVBT, and a slightly better correlation between platelet count and IVBT. In conclusion, BC-PCs showed a slightly higher CCI and a better response in IVBT than A-PCs. No statistical difference was demonstrated between BC-PCs and A-PCs transfused within 2 days after donation, with respect to function and recovery in vivo. BC-PCs stored for 3 days or more showed about the same CCI and IVBT as stored A-PC but significantly lower CCI and higher IVBT than fresh BC-PCs. This may indicate that the preparation and/or storage conditions were not optimal. IVBT seems to be a useful possibility to test the in vivo behavior of transfused platelets.
Adolescent↗