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Biomedical subjects

A Mertens

Publications and source records attributed to A Mertens.

At least 19 recordsLinked to original sources
PubMed1993

Selective non-nucleoside HIV-1 reverse transcriptase inhibitors. New 2,3-dihydrothiazolo[2,3-a]isoindol-5(9bH)-ones and related compounds with anti-HIV-1 activity.

A series of substituted 2,3-dihydrothiazolo[2,3-a]isoindol-5(9bH)-ones and related compounds 1-73 were synthesized and evaluated for their ability to inhibit reverse transcriptase (RT) of the human immune deficiency virus 1 (HIV-1) and replication of HIV-1 in MT2 cells. The antiviral activity of these compounds depends on the stereoselective configuration of the substituent in position 9b. Structure-activity studies were done within these series of compounds to determine the optimum substituents for antiviral activity. The most potent inhibitors were found in the class of 2,3-dihydrothiazolo[2,3-a]isoindol-5(9bH)-ones bearing a phenyl ring system in position 9b optionally substituted with one or two methyl groups or a chlorine atom in position 8. The most active analogues (R)-(+)-1, (R)-(+)-6, (R)-(+)-13, (R)-(+)-26, and (R)-(+)-53 inhibit the HIV-1 RT with an IC50 between 16 and 300 nM and an IC50 between 10 and 392 nM in MT2 cells, respectively.

Animals↗
PubMed1993

Non-nucleoside inhibitors of HIV-1 reverse transcriptase: molecular modeling and X-ray structure investigations.

The structural features of a new class of non-nucleoside HIV-1 reverse transcriptase inhibitors (3) are presented. Comparison of the structural and electronic properties with those of TIBO (1) and Nevirapine (2) yields a common three-dimensional model. This model permits the improvement of the lead compound 3 by chemical modification (5,6). Additionally, two new types of inhibitors (4, 7) with similar biological activity can be derived from this model. The structure of the new compounds, including their absolute configuration, are determined by X-ray crystallography.

Benzodiazepines↗
PubMed1993

Final height after treatment for childhood acute lymphoblastic leukemia: comparison of no cranial irradiation with 1800 and 2400 centigrays of cranial irradiation.

We analyzed growth and final heights in 127 patients (68 female patients) treated for childhood acute lymphoblastic leukemia. Central nervous system prophylaxis included either no cranial radiation therapy (CRT) (n = 38), irradiation with 1800 centigrays (cGy) (n = 36), or irradiation with 2400 cGy (n = 53). None of the patients received spinal irradiation. Mean (+/- SEM) age at diagnosis was 6.4 +/- 0.25 years, mean height standard deviation score (SDS) at diagnosis was 0.28 +/- 0.12, and mean age at final height was 18.26 +/- 0.19 years. The change in height SDS between diagnosis and achievement of final height was significant for all treatment groups: -0.49 +/- 0.14, no CRT; -0.65 +/- 0.15, 1800 cGy; and -1.38 +/- 0.16, 2400 cGy. Irradiated patients had a greater loss in height SDS compared with the nonirradiated patients (p < 0.01), and those treated with 2400 cGy CRT had a greater decrease in final height SDS than the patients treated with 1800 cGy (p < 0.01). Both younger age and female sex were significantly associated with a greater decrease in height SDS in the patients treated with CRT; girls < or = 4 years of age at diagnosis had a mean loss in height SDS that was more than twice that observed for others treated with the same dose of CRT. Thus, although modern regimens for acute lymphoblastic leukemia (no CRT or 1800 cGy CRT) appear overall to have only a modest impact on final height, patients, especially girls, treated with 1800 cGy CRT at a young age remain at risk for clinically significant growth failure.

Age Factors↗
PubMed1993

Second tumors after treatment of childhood malignancies.

The occurrence of a second malignancy represents a serious complication of childhood cancer. With the introduction of more intensive multiagent therapy for childhood cancers, not only are a greater proportion of children surviving their initial cancer, but also they now may be at greater risk for developing a second malignancy. The larger studies indicate that the cumulative incidence of second cancers may be as high as 12% at 20 years following the initial cancer. The most consistent finding of the larger studies is that the elevated risk of a second cancer remains relatively constant over time, but the absolute risk increases substantially as the length of follow-up increases. There are treatment-related risk factors, such as solid tumors within irradiated fields and secondary leukemias following alkylating therapy. Retinoblastoma represents one example of the role of genetic predisposition in second cancers. It is imperative that survivors of childhood cancer be closely followed to determine the occurrence of second cancers, particularly those that may occur many years following the original childhood cancer. Research needs to be directed toward the identification of treatment, as well as genetic and life style risk factors. Intervention, through modifications of treatment protocols and implementation of preventive programs, may have a future role in reducing the occurrence of second cancers.

Age Factors↗
PubMed1990

Nonsteroidal cardiotonics. 3. New 4,5-dihydro-6-(1H-indol-5-yl)pyridazin-3(2H)-ones and related compounds with positive inotropic activities.

A series of substituted indolyldihydropyridazinones and related compounds 1-18 were synthesized and evaluated for positive inotropic activity. In rats, most of these indole derivatives produced a dose-related increase in myocardial contractility with little effect on heart rate and blood pressure. Compound 13, 4,5-dihydro-5-methyl-6-(2-pyridin-4-yl-1H-indol-5-yl)pyrazin-3(2H) -one (BM 50.0430), was further investigated in cats. The increase in contractility in this animal model was not mediated via stimulation of beta-adrenergic receptors. After oral administration of 1 mg/kg to conscious dogs, compound 13 and pimobendan were still active after 6.5 h. However, the cardiotonic effect of 13 was at least 2-fold that of pimobendan after this period of time. The structural requirements necessary for optimal cardiotonic activity within this novel class of indole derivatives are a heterocyclic aromatic ring in position 2, a hydrogen or a methyl group in position 3, and a dihydropyridazinone ring system in position 5 of the indole.

Animals↗
PubMed1989

Nonsteroidal cardiotonics. 2. The inotropic activity of linear, tricyclic 5-6-5 fused heterocycles.

We previously reported the structure-activity relationships (SAR) of adibendan (1), a potent and long-acting cardiotonic. This paper describes the synthesis of a novel series of linear, tricyclic fused heterocycles of the 5-6-5 type. The compounds were evaluated for positive inotropic activity in anesthetized rats, cats, and dogs. Changes in left ventricular dP/dt were measured as an index of cardiac contractility. The increase in contractility was not mediated via stimulation of beta-adrenergic receptors. The data revealed the intrinsic positive inotropic activity of the parent compound of this series, 5,7-dihydro-7,7-dimethylpyrrolo[2,3-f]benzimidazol-6(1H)-one (2). The structural features that impart optimal inotropic activity are presented and compared with those of the 4,5-dihydro-3(2H)-pyridazinone series. The most potent compounds were evaluated orally in conscious dogs with implanted Konigsberg pressure transducers to measure ventricular pressures, and their effect on left ventricular dP/dt was compared with that of 1, pimobendan, and indolidan. After administration of 1 mg/kg, 1, 3, 7, 19, 22, 24, 31, 54, pimobendan, and indolidan were equipotent, but only with 1, 31, pimobendan, and indolidan, durations of action exceeded 6 h.

Animals↗
PubMed1987

Incidence and bacterial aetiology of neonatal conjunctivitis.

Two hundred and twenty-nine infants born consecutively at the maternity ward of the Middelheim Hospital in Antwerp, over a period of 5 months, and an additional 55 randomly selected infants born at the same hospital were clinically and microbiologically investigated before leaving the maternity ward. All infants born at this maternity ward received argyrol eye drops immediately after birth. Twenty-six (11%) of the infants consecutively investigated had neonatal conjunctivitis diagnosed before leaving the maternity ward, where they stayed from 7-10 days. Another 29 infants were reported to have developed sticky eyes and/or red eyes after leaving the maternity hospital and before 1 month of age. The instantaneous risk of developing, a conjunctivitis was equal for each day of the first month of life. Chlamydia trachomatis was isolated from the eyes of 11 of the 229 (4.8%) consecutively born infants but only one had conjunctivitis symptoms before leaving the maternity ward. Overall one or more bacterial species could be isolated from the eyes of 143 (48%) of the infants, but only viridans streptococci and Staphylococcus aureus were cultured significantly more often from the eyes of cases with conjunctivitis than from the eyes of the infants without conjunctivitis (P less than 0.001).

Bacteria↗
PubMed1987

Nonsteroidal cardiotonics. 1. 2-Pyridyl-6,7-dihydro-3H,5H-pyrrolo[2,3-f]benzimidazol-6-ones, a novel class of cardiotonic agents.

A series of substituted 2-pyridyl-6,7-dihydro-3H,5H-pyrrolo[2,3-f]benzimidazol-6-ones 1-24 were synthesized and evaluated for positive inotropic activity. In rats, cats, and dogs most of these tricyclic heterocycles produced a dose-related increase in myocardial contractility with little effect on heart rate and blood pressure. The increase in contractility was not mediated via stimulation of beta-adrenergic receptors. Compound 1 (BM 14.478) was more potent than milrinone (25) and enoximone when administered intravenously to rats, cats, and dogs. After oral administration of 1 mg/kg, compound 1, milrinone, and pimobendan were equipotent. However, only 1 and pimobendan were still active after 6 h. The structural requirements necessary for optimal cardiotonic activity within this novel class of heterocycles were investigated.

Animals↗
PubMed1982

[The accident law].

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Accidents, Occupational↗
PubMed1979

Halophilic, lactose-positive Vibrio in a case of fatal septicemia.

A halophilic Vibrio species was isolated from blood cultures from a 59-year-old male with enteritis. The strain differed from Vibrio parahaemolyticus and Vibrio alginolyticus by its ability to ferment lactose, its production of beta-galactosidase, and its lower NaCl tolerance. A report of this infection and a description of the isolate is presented.

Blood↗