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Biomedical subjects

M Kroll

Publications and source records attributed to M Kroll.

At least 19 recordsLinked to original sources
PubMed2001

Thyroid function in healthy and sick very-low-birth-weight infants--thyrotropin and free thyroxine levels until the sixth week of age.

Hypothyroxinemia in preterm infants without congenital hypothyroidism is associated with developmental delay. Longitudinal information on thyroid function in very-low-birth-weight (VLBW, <1,500 g birth weight) infants is limited: we present data on thyroid function in sick and healthy VLBW infants until 6 weeks of age. Free T(4) and TSH levels routinely obtained on days 14-21 and days 35-49 in 92 consecutive VLBW infants were correlated retrospectively with neonatal morbidity. Free T(4) levels were positively correlated with gestational age; an independent effect of neonatal disease on thyroid function was not detectable.

Aging↗
PubMed2000

Inducible NF-kappaB activation is permitted by simultaneous degradation of nuclear IkappaBalpha.

Signal-induced phosphorylation and ubiquitination of IkappaBalpha targets this inhibitor of NF-kappaB for proteasome-mediated degradation, thus permitting the release of active NF-kappaB. Upon cell stimulation, NF-kappaB activation results in neotranscription and neosynthesis of its own inhibitor, IkappaBalpha. As reported earlier, the neosynthesized inhibitor is then accumulated in the nucleus, where it rapidly binds to and terminates the function of nuclear NF-kappaB upon withdrawal of the stimulus. The present work was aimed at understanding how NF-kappaB activity is preserved while stimuli persist, despite intense, simultaneous IkappaBalpha neosynthesis, which would be expected to end NF-kappaB activity. We here show that incoming IkappaBalpha in the nucleus represents a target for resident nuclear proteasome complexes. Signal-induced, proteasome-dependent degradation of phosphorylated and ubiquitinated IkappaBalpha occurs in the nucleus, thus permitting the onset and persistence of NF-kappaB activity as long as stimulation is maintained. Our results suggest that intranuclear proteolysis of IkappaBalpha is necessarily required to avoid self-termination of NF-kappaB activity during cell activation.

Cell Nucleus↗
PubMed2000

ICD waveform optimization: a randomized, prospective, pair-sampled multicenter study.

The theoretical tissue model-based estimates of phase 1 and phase 2 duration of biphasic waveforms are considerably shorter than the pulse widths currently used in ICDs with standard tilt. This study used a tissue resistance/capacitance (RC) model to identify optimal biphasic pulse widths. By paired step-down defibrillation threshold (DFT) testing, the efficacy of standard versus "tuned" biphasic waveforms was evaluated in 91 patients. Standard waveforms consisted of a phase 1 set to 65% tilt and phase 2 = phase 1. The tuned waveform was based on an RC model of membrane characteristics with a time constant of 3.5 ms. The optimal phase 1 truncation point is at the peak of membrane response. The optimal phase 2 duration ends with a membrane response near or just below 0. In paired analysis, no significant differences were found in DFT or impedance between standard and tuned waveforms. In patients with DFTs > 400 V, the tuned waveform lowered the DFT by an average of 38 V (P < 0.05). Multivariate analyses showed a significant inverse relationship between DFT and impedance (P < 0.001). As impedance increased, the tuned waveform was associated with DFTs comparable to the standard waveform with shorter pulse duration and lower delivered energy. No single tilt value allowing an easy calculation of delivered energy was related to ICD waveform efficacy. The use of ICDs with tuned optimal pulse durations offer a greater flexibility of choice for patients with high DFTs.

Aged↗
PubMed2000

Thyroid function in very low birthweight infants after intravenous administration of the iodinated contrast medium iopromide.

BACKGROUND: Thyroid function disorders have often been observed in preterm infants after intravenous administration of iodinated contrast medium. The effect on thyroid function depends on the dosage, but the choice of the contrast medium may be equally important, as there are appreciable pharmacological differences between them. METHOD: Thyroid function was analysed in 20 very low birthweight infants of gestational age less than 30 weeks after injection of iopromide, a monomeric non-ionic iodinated contrast medium. Levels of free thyroxine and thyroid stimulating hormone were compared with those in 26 control infants. RESULTS: Free thyroxine levels in all study infants ranged from 9.0 to 25.7 pmol/l (days 14-21) and 9.0 to 23.2 pmol/l (days 35-49), and thyroid stimulating hormone levels ranged from 0.13 to 0.26 mU/l (days 14-21) and 0.26 to 11.11 mU/l (days 35-49). These levels were not altered after injection of iopromide. CONCLUSION: The risk of transient hypothyroidism or hyperthyrotropinaemia may be reduced with the use of iopromide compared with other contrast media.

Case-Control Studies↗
PubMed2000

Missouri practitioners show notable improvement in diabetic kidney disease screenings.

Missouri practitioners participating in a cooperative Diabetic Kidney Disease Project, organized by the Missouri PRO, showed significant improvement in screening for nephropathy among diabetic patients following a quality improvement intervention. This project provides a solid basis for the National Diabetes Project initiated by HCFA as part of the PRO's Sixth Statement of Work.

Diabetic Nephropathies↗
PubMed1999

Prescription attitudes among gynecologists towards two particular risk factors of osteoporosis: the patient's age and her bone mineral density.

OBJECTIVE: The present report assesses, among Belgian gynecologists, the effect of age and bone mineral density on osteoporosis prescription strategy in postmenopausal women. METHODS: Charts of postmenopausal women were summarized. We constructed cases by modifying some parameters. Ten years of age were added or subtracted to the real age of the patient. The bone mineral density (BMD) result was also modified (three levels: normal BMD, osteopenia, osteoporosis). A total of 612 cases were constructed. Twelve cases were sent out of these 612 files to every Belgian gynecologist (n = 1010). For each chart the gynecologists were asked whether they would treat the patient with HRT. They were also asked whether they would prescribe other therapies than HRT and if so, which ones. RESULTS: The chance to have an osteoporosis prevention or treatment prescribed increased when BMD decreased (respectively 57.4% for normal BMD, 73.1% for osteopenia cases and 89.4% for osteoporosis cases; P < 0.001). HRT was the most frequently prescribed medication (67% of the cases), but its prescription rate does not reflect only osteoporosis prevention. Nevertheless, for similar cases with osteopenia, the HRT prescription rate increased by a factor 1.25 and for similar cases with osteoporosis, HRT prescription rate increased by a factor 1.39. Calcium was the 2nd most frequent prescribed regimen. It was prescribed in 17% of the cases. A 3.4-fold increase for osteopenia cases and 7.6-fold increase for osteoporosis cases was observed, compared to women with normal BMD. When calcium was prescribed, it was in association with HRT in 64% of the osteopenia cases and in 76% of osteoporosis cases. Other drugs were less often prescribed. For the "younger age group", that is, with a mean age of 55 years, a prescription rate of 82.9% for any osteoporosis regimen was reached, whereas in the age group that was 10 years older a 20% lower prescription rate was reached (62.6%, P < 0.001). This was mostly due to a decrease in HRT prescription. CONCLUSIONS: Prescription of medication known to reduce osteoporosis occurred more often in cases with low BMD. In the older patients with osteoporosis, gynecologists prescribed HRT less frequently. This was not compensated by a higher prescription rate of other medication.

Adult↗
PubMed1999

Inducible degradation of IkappaBalpha by the proteasome requires interaction with the F-box protein h-betaTrCP.

Activation of NF-kappaB transcription factors requires phosphorylation and ubiquitin-proteasome-dependent degradation of IkappaB proteins. We provide evidence that a human F-box protein, h-betaTrCP, a component of Skp1-Cullin-F-box protein (SCF) complexes, a new class of E3 ubiquitin ligases, is essential for inducible degradation of IkappaBalpha. betaTrCP associates with Ser32-Ser36 phosphorylated, but not with unmodified IkappaBalpha or Ser32-Ser36 phosphorylation-deficient mutants. Expression of a F-box-deleted betaTrCP inhibits IkappaBalpha degradation, promotes accumulation of phosphorylated Ser32-Ser36 IkappaBalpha, and prevents NF-kappaB-dependent transcription. Our findings indicate that betaTrCP is the adaptor protein required for IkappaBalpha recognition by the SCFbetaTrCP E3 complex that ubiquitinates IkappaBalpha and makes it a substrate for the proteasome.

Cell Cycle Proteins↗
PubMed1999

The secondary fungal metabolite gliotoxin targets proteolytic activities of the proteasome.

BACKGROUND: The fungal epipolythiodioxopiperazine metabolite gliotoxin has a variety of toxic effects such as suppression of antigen processing, induction of macrophagocytic apoptosis and inhibition of transcription factor NF-kappaB activation. How gliotoxin acts remains poorly understood except that the molecule's characteristic disulfide bridge is important for immunomodulation. As this fungal metabolite stabilizes the NF-kappaB inhibitor IkappaBalpha in the cytoplasm, we decided to investigate its molecular mechanism of action. RESULTS: We show that gliotoxin is an efficient, noncompetitive inhibitor of the chymotrypsin-like activity of the 20S proteasome in vitro. Proteasome inhibition can be reversed by dithiothreitol, which reduces gliotoxin to the dithiol compound. In intact cells, gliotoxin inhibits NF-kappaB induction through inhibition of proteasome-mediated degradation of IkappaBalpha. CONCLUSIONS: Gliotoxin targets catalytic activities of the proteasome efficiently. Inhibition by gliotoxin may be countered by reducing agents, which are able to inactivate the disulfide bridge responsible for the inhibitory capacity of gliotoxin.

Cells, Cultured↗
PubMed1999

Bringing together nursing and law: a fitting combination in today's health care environment.

Blending careers is an exciting alternative to choosing one profession or another. In this article, the author relates her experiences as a nurse to her current choice of profession, the law. The author used the same principles and interventions developed while nursing in dealing with clients experiencing personal injuries, working on the estate of a client's deceased family member, or helping a client with the many issues that arise with the end of a marriage. The marriage of nursing and law has been a successful partnership. One career builds on the experience and education of the other, allowing the practitioner to offer clients a total package of legal and health care delivery assistance.

Career Mobility↗
PubMed1998

Case-control studies of relation between childhood cancer and neonatal vitamin K administration.

OBJECTIVE: To investigate the possible link between neonatal administration of intramuscular vitamin K and childhood cancer. DESIGN: Matched case-control study. SETTING: Selected large maternity units in England and Wales. SUBJECTS: Children with cancer born 1968-85, diagnosed 1969-86; controls matched for sex, month of birth, and hospital of birth. MAIN EXPOSURE MEASURES: Neonatal administration of vitamin K, length of gestation, birth weight, type of delivery, admission to special care baby unit. RESULTS: After exclusion of cases with missing notes or unknown hospital vitamin K policy, 597 cases and matched controls were studied. Written records on the use of vitamin K were available for only about 40% of these, and to avoid possible bias from selective recording it was assumed that the stated hospital policy was followed. The association between cancer generally and intramuscular vitamin K was of borderline significance (odds ratio 1.44, P = 0.05); the association was strongest for leukaemia. There was, however, also an effect of abnormal delivery, which could explain some of the findings. CONCLUSIONS: The lack of consistency between the various studies so far published, including this one, and the low relative risks found in most of them suggest that the risk, if any, attributable to the use of vitamin K cannot be large, but the possibility that there is some risk cannot be excluded. A comparison of the predicted consequences of various policies shows that even a 10% increase would imply that prophylaxis using the commonly recommended 1 mg intramuscular dose should be restricted to babies at particularly high risk of vitamin K deficiency bleeding; alternatively a lower dose might be given to a larger proportion of those at risk.

Adolescent↗
PubMed1998

Ecological studies of relation between hospital policies on neonatal vitamin K administration and subsequent occurrence of childhood cancer.

OBJECTIVE: To investigate the possible link between neonatal administration of intramuscular vitamin K and childhood cancer. DESIGN: Ecological studies comparing incidence of cancer in groups of children classified by the vitamin K policy in operation at their hospital of birth. SETTING: Selected large maternity units in England, Scotland, and Wales. SUBJECTS: Children born in these units in varying periods between 1966 and 1991. MAIN OUTCOME MEASURES: Cancer occurring among these children before age 15 years identified by using the National Registry of Childhood Tumours. Ratios of observed to expected numbers of these conditions calculated for hospitals where the policy was to give all babies intramuscular vitamin K (non-selective) and where the policy was to use this treatment only for a selected minority of babies at increased risk of vitamin K deficiency bleeding (selective). RESULTS: These ratios were calculated for children born in 94 hospitals with varying vitamin K policies. A raised risk was occasionally associated with vitamin K, but the overall results were not significant, and there was no evidence to support the previously suggested doubling of the risk of childhood cancer. CONCLUSIONS: On the basis of the results reported here it is unlikely that there is a greatly increased risk of childhood cancer attributable to intramuscular vitamin K given to newborns, if indeed there is any.

Adolescent↗
PubMed1998

Engineering of betabellin-15D: a 64 residue beta sheet protein that forms long narrow multimeric fibrils.

The betabellin target structure is a beta-sandwich protein consisting of two 32 residue beta-sheets packed against one another by interaction of their hydrophobic faces. The 32 residue chain of betabellin-15S (HSLTAKIpkLTFSIAphTYTCAV pkYTAKVSH, where p=DPro, k=DLys, and h=DHis) did not fold in water at pH 6.5. Air oxidation of betabellin-15S provided betabellin-15D, the 64 residue disulfide bridged two-chain molecule, which also remained unfolded in water at pH 6.5. By circular dichroic spectropolarimetry, the extent of beta structure observed for betabellin-15D increased with the pH and ionic strength of the solution and the betabellin-15D concentration. By electron microscopy, in 5.0 mM MOPS and 0.25 M NaCl at pH 6.9, betabellin-15D formed long narrow multimeric fibrils. A molecular model was constructed to show that the dimensions of these betabellin-15D fibrils are consistent with a single row of beta-sandwich molecules joined by multiple intersheet H-bonds.

Amino Acid Sequence↗
PubMed1998

Detection of CBFbeta/MYH11 fusion transcripts in patients with inv(16) acute myeloid leukemia after allogeneic bone marrow or peripheral blood progenitor cell transplantation.

We evaluated the occurrence of the CBFbeta/MYH11 fusion transcripts by PCR analysis in 10 patients with inv(16)(p13;q22) acute myeloid leukemia (AML) who underwent allogeneic bone marrow transplantation (BMT) (n = 5), peripheral blood progenitor cell transplantation (PBPCT) (n = 3), or autologous transplantation (n = 2). In addition to the analysis of minimal residual disease (MRD), the chimerism status of patients after allogeneic transplant was studied by PCR. The CBFbeta/MYH11 fusion transcript was not detectable in six of seven patients who remained in remission after allogeneic BMT or PBPCT. Two of these patients in remission were monitored for 50 months and 64 months post-BMT. One patient in remission was PCR-positive for CBFbeta 3 months post-BMT in a single BM sample, but not in a simultaneously examined blood sample, suggesting that analyses from BM samples are more sensitive than those from blood samples. Sequential PCR assays performed 6 and 12 months post-BMT obtained from the same patient were negative. Another patient with a positive PCR assay 3 months post-allogeneic PBPCT, remained PCR positive for the CBFbeta/MYH11 fusion transcript when tested 6 months post-PBPCT. A chimerism analysis by PCR revealed a mixed chimerism status in this patient. He relapsed 7 months post-transplant. Before transplant, in all nine patients who were in complete remission of AML (eight patients in 1CR, one patient in 2CR), the CBFbeta/MYH11 transcript was detectable. In one patient in relapse, the fusion transcript was not only detectable in blood and bone marrow, but also in a cerebrospinal fluid sample prior to transplant. Two patients who received autologous BMT were monitored for CBFbeta/MYH11 transcripts 3 months after BMT. The CBFbeta/MYH11 was detected in these patients. Both patients subsequently relapsed 3 months and 23 months post-autologous BMT. The results study show that analysis of the CBFbeta/MYH11 fusion transcript by PCR seems to be a suitable method for monitoring minimal residual disease in AML patients with inv (16).

Adolescent↗
PubMed1998

Educating patients about the benefits and drawbacks of hormone replacement therapy.

Hormone replacement therapy (HRT) influences many aspects of health: climacteric symptoms, osteoporosis, cardiovascular disease, breast and endometrial cancer, thrombosis and emboli, and Alzheimer's disease. A decision to use HRT may depend on a woman's individual views of the menopausal transition, the postmenopause and its consequences. It is therefore useful that the health provider inquiries about and discusses these issues in a cultural and family context. Health providers and patients should be thoroughly informed about the symptoms associated with hormonal deprivation, the associated risks of osteoporosis and cardiovascular disease, and the potential of HRT to prevent these afflictions. Recent studies suggest that HRT might be particularly beneficial in women who have an increased risk for cardiovascular disease (because of left ventricular hypertrophy, diabetes mellitus, hypertension or hypercholesterolaemia, or because they smoke) or osteoporosis. In women who are undecided about HRT, a low bone mineral density measurement might help convince them to start using, or to continue using, HRT. There is also a need to discuss with the patient the effect of HRT on cancer risk. In most instances, women can be reassured about the risk of endometrial cancer. The risk of breast cancer should be carefully considered and discussed with each patient before beginning HRT. In most cases, HRT should not be withheld because of fears about breast cancer, because the protective effects of HRT against cardiovascular disease and osteoporosis outweigh the possible increased risk of breast cancer. When HRT is prescribed, individual regiments should be discussed with the patient, who must be warned of the possible adverse effects. In older women, HRT can be started at half the normal dosage and tolerability assessed before increasing the dosage further.

Age Factors↗
PubMed1998

[Pharmacoeconomics of menopause treatments: epidemiological data and hormonal and non-hormonal prescription attitude of Belgian gynecologists].

In an economic analysis one has not only to consider costs induced by hormonal substitution therapy (HRT) but also its impact health. Different therapy costs will be considered and related to potential benefits on health. HRT decreases the incidence of symptoms of the menopause, the risk of osteoporosis and perhaps the incidence of coronary hearth disease and the risk of Alzheimer disease but probably increases the incidence of breast cancer. For a majority of women, the favorable impact seems to dominate, increasing their life expectancy.

Aged↗