Search PubMed⌕ Search

Biomedical subjects

A Kaiser

Publications and source records attributed to A Kaiser.

At least 19 recordsLinked to original sources
PubMed2006

Prognosis of women with pelvic pain during pregnancy: a long-term follow-up study.

STUDY DESIGN: A follow-up study of women with pelvic pain during pregnancy. OBJECTIVES: To evaluate prognostic factors for pelvic pain. METHODS: Out of a cohort of 870 pelvic pain patients, 598 women, who delivered less than 42 months prior to the follow-up measurement, were selected for follow-up. RESULTS: Data of 430 women were available for analysis with a mean follow-up duration of 18 months postpartum. Forty-three women still experienced moderate or severe pain and were seriously hindered in more than one activity. At intake symptomatic women experienced a higher overall severity of complaints, more walking deficiencies, and mentioned prepregnancy back pain more often and reported labor lasting longer than 18 h 2.5 times more often than asymptomatic women. Explained variance of these factors is small. CONCLUSIONS: Mean 18 months postpartum a small group had moderate or severe pain. Prepregnancy back pain, severity of complaints, and number of walking deficiencies at primary referral as well as duration of labor showed a significant relation with symptoms.

Adult↗
PubMed2004

Pelvic pain during pregnancy: a descriptive study of signs and symptoms of 870 patients in primary care.

STUDY DESIGN: The authors conducted a cross-sectional analysis. OBJECTIVE: The objective of this study was to describe the signs and symptoms of pregnant women with pain and dysfunction in the pelvic area. SUMMARY OF BACKGROUND DATA: Pelvic pain during pregnancy is common with incidence rates of 48% to 56%. The exact cause of pelvic pain during pregnancy is still unclear. Also unclear is the association between physical examination and the occurrence of pelvic pain during pregnancy. METHODS: Pregnant women with pelvic pain were sent for treatment to 2 physical therapy practices between January 1997 and January 2002. A standardized clinical examination protocol and an extensive questionnaire were used to obtain relevant clinical and demographic characteristics. RESULTS: In total, 870 women were included. The average score of the overall severity of the complaints was 7.8 (scale 0-15). Main complaints were located around the sacroiliac joints (76.6%) and the pubic symphysis (57.2%). The area of pain was not related to positive signs in passive hip movements and sacroiliac tests. The highest positive test results were found for Patrick sign (71.7%), active straight leg raise (ASLR) test (66.4%), resisted adduction (54.4%), and passive hip abduction (36.9%). Overall severity of complaints was related to age, number of weeks pregnant, passive hip flexion and internal rotation, and swimming. The total explained variance of these factors was 15.9%. No relationship was found between overall complaints and sacroiliac tests, pelvic pain during a previous pregnancy, extremely painful or type of previous deliveries. CONCLUSIONS: Pregnant patients with pelvic pain show a considerable level of complaints. The overall severity of complaints is not related to previous peripartum pelvic pain or type of deliveries or to commonly used tests. Further study on the role of clinical examination, including passive flexion and internal rotation of the hip joints, is recommended.

Adolescent↗
PubMed2004

The efficacy of inhibitors involved in spermidine metabolism in Plasmodium falciparum, Anopheles stephensi and Trypanosoma evansi.

In the present study, we have tested the effect of different polyamine inhibitors of the spermidine metabolizing enzymes deoxyhypusine synthase and homospermidine synthase in different chloroquine resistant Plasmodium falciparum strains, in the mosquito Anopheles stephensi (Diptera: Culicidae) and in a Trypanosoma evansi clone I from strain STIB 806 K China. Recent experiments have shown that agmatine is a growth inhibitor of the malaria parasite P. falciparum (Kaiser et al. 2001) in vitro. A comparison of agmatine efficacy with the new antimalarials artemisinin, triclosan and conventional chloroquine showed similar or even better results on the basis of growth inhibition and the reduction of developmental forms. However, no effect of triclosan or agmatine was observed at the ribonucleic acid level. In a second set of experiments, we tested the effect of 1,7-diaminoheptane and agmatine on oocyst formation in A. stephensi after infection with Plasmodium yoelii. Agmatine had an antisporozoite effect since 1,000 microM led to a 59.5% inhibition of oocysts. A much weaker inhibitor of oocyst formation was 1,7-diaminoheptane. The most effective in in vitro inhibition of T. evansi was dicyclohexylamine, an inhibitor of spermidine biosynthesis with an IC(50 ) value of 47.44 microM and the deoxyhypusine inhibitor 1,7-diaminoheptane with an IC(50) value of 47.80 microM. However, both drugs were ineffective in in vivo experiments in a Trypanosoma mouse model. Two different spermidine analogues, 1,8-diaminooctane and 1,3-diaminopropane with IC(50) values of 171 microM and 181.37 microM, respectively, were moderate inhibitors in vitro and ineffective in vivo.

Animals↗
PubMed2003

Targeting enzymes involved in spermidine metabolism of parasitic protozoa--a possible new strategy for anti-parasitic treatment.

Sequencing data obtained from the Plasmodium, Anopheles gambiae and human genome projects provide a new basis for drug and vaccine development. One of the most characteristic features in the process of drug development against parasitic protozoa is target identification in a biological pathway. The next step must be a structure-based rational drug design if the target is not only present in the parasite. In mouse models of malaria, such drugs should be tested for efficacy of the new therapies. Here, we present data that pinpoint the existence of two enzymes of the polyamine pathway involved in spermidine metabolism in P. falciparum, i.e. deoxyhypusine synthase (DHS; EC 1.1.1.249) and homospermidine synthase (HSS; EC 2.5.1.45). Recent data obtained from the malaria genome databases showed that at least a putative gene encoding DHS is present in the parasite. Sequencing data from the P. falciparum genome project prove that the eukaryotic initiation factor eIF5A (the substrate for DHS) exists in P. falciparum. Here, we present the amino acid sequence of eIF5A from P. vivax, which causes tertiary malaria. EIF5A from P. vivax shows 82% nucleic acid and 97% amino acid identity to its homologue from P. falciparum. GC/MS data and inhibitor studies with agmatine prove that the triamine homospermidine occurs in the parasite. These data suggest a separate locus encoding HSS in P. falciparum. The hss gene recruits from the dhs gene in eukaryotes. Here, we present genomic DNA fragments obtained by amplification with primers of a conserved region (amino acid positions 550-1,043) between the putative P. falciparum DHS gene ( dhs) and the HSS gene ( hss) from the plant Senecio vulgaris (Asteraceae). The amplification product from different P. falciparum strains reveals differences in sequence identity, compared with the putative dhs gene from P. falciparum strain 3D7. Expression of the full-length clone and determination of HSS-specific activity will finally prove whether a separate region encoding HSS exists.

Alkyl and Aryl Transferases↗
PubMed2003

Outcome after treatment of coronary in-stent restenosis; results from a systematic review using meta-analysis techniques.

AIMS: To evaluate the clinical outcome after treatment of coronary in-stent restenosis. METHODS AND RESULTS: For identification of the relevant literature a specific search strategy was conducted and explicit inclusion criteria were defined to avoid selection bias. Based on the selected literature, a systematic review using descriptive statistics and meta-analysis methods regarding the outcome after treatment of coronary in-stent restenosis was performed. The proportion of patients experiencing a major adverse cardiac event (MACE) as defined by death, myocardial infarction, and target lesion revascularization was the main outcome measure. A total of 1304 citations were identified. Among these, 28 studies (six different treatment modalities) including a total of 3012 patients met the inclusion criteria and were incorporated into this analysis. The estimated average probability of experiencing a major cardiac adverse event after treatment for in-stent restenosis with a follow-up period of 9+/-4 months was 30.0% (25.0-34.9%, 95% confidence interval) with strong evidence for heterogeneity between study specific results (P=0.0001). The clinical outcome was not significantly different between treatment modalities. After adjustment for confounding factors (i.e. lesion length), however, patients undergoing intracoronary radiation showed an estimated advantage of 16.9% (-37.7+/-4.0%, 95% confidence interval) in MACE free survival, as compared to balloon angioplasty. The post-interventional diameter stenosis was the only independent predictor for the long-term outcome after treatment of in-stent restenosis. CONCLUSIONS: Treatment of in-stent restenosis is associated with an overall 30% rate of major adverse cardiac events. Currently, repeat angioplasty is the treatment option of choice, especially when a sufficient acute procedural result can be achieved. Intracoronary radiation should be considered in cases with therapy refractory forms of diffuse in-stent restenosis.

Coronary Restenosis↗
PubMed2002

[Epithelioid hemangioendothelioma of the heart in association with myelodysplastic syndrome].

The case of a primary cardiac epithelioid hemangioendothelioma (EHE) arising multifocally in the papillary muscle of the tricuspid valve and the deeper trabecular muscle in a 68-year-old male with myelodysplastic syndrome is presented. The tumor was an incidental autopsy finding. Histologically the tumor is characterized by proliferation of plump epithelial-like endothelial cells with the vascular differentiation being mostly expressed at a cellular level in the form of cytoplasmic vacuoles. In the differential diagnosis, metastatic carcinoma, cardiac myxoma as well as other epithelioid vascular neoplasms should be considered. EHEs are indolent tumors of intermediate malignancy with the potential to metastasize, even after a long time. Primary cardiac EHE is extremely rare. To our knowledge, only four EHEs of the heart have been reported in the literature. We believe, this is the first report of a cardiac EHE in this localization and the first one in association with myelodysplastic syndrome.

Aged↗
PubMed2002

The adenoma-carcinoma sequence applies to epithelial tumours of the papilla of Vater.

Adenomas of the papilla of Vater are relatively rare tumours. They are of particular interest, not only because of their particular topography, but also because the adenoma-carcinoma sequence - accepted in the colorectum - has also been postulated to apply to the papilla of Vater. In fact, ampullary adenoma is often considered to be a precancerous lesion. To investigate this hypothesis, we reviewed the surgical specimens obtained during Whipple's procedures carried out to treat histologically confirmed carcinoma of the ampulla. A total of 37 surgical specimens obtained since January 1991 were reexamined for the presence of coexisting adenomatous structures. Such adenomatous residues were confirmed in 24/37 (65 %) cases. In 13/37 (35 %) cases, no residual adenoma was found. A comparison of the two groups revealed that detection of coexisting adenomatous structures decreased with increasing tumour progression. In similar manner, this also applied to the degree of malignancy: with increasing grade of malignancy the rate of detectable adenomatous structures decreased significantly. It may be assumed that these observations are due to the 'overgrowth' of preexisting adenomas by carcinomatous tissue. Further evidence is provided by the histological observation of transitional stages from adenoma with mild, moderate and severe cellular atypia to invasive carcinoma. These findings support the hypothesis of an adenoma-carcinoma sequence.

Adenoma↗
PubMed2002

The necessity to develop drugs against parasitic diseases.

This review focuses on the most significant trends in the development of drugs for the treatment of malaria, African sleeping sickness and toxoplasmosis. In the case of malaria, those include new fixed-dose artemisinin combinations, antifolates and new targets in the apicoplast of Plasmodium falciparum. Targets in the treatment of trypanosomiasis are the biosynthesis of glycosylphosphatidylinositol and enzymes involved in the biosynthesis of trypanothione. Efforts to develop a vaccine against toxoplasmosis are discussed as well.

Animals↗
PubMed2001

Injury-induced apoptosis of neurons in adult brain is mediated by p53-dependent and p53-independent pathways and requires Bax.

The mechanisms of injury-induced apoptosis of neurons within the CNS are not understood. We used a model of cortical injury in rat and mouse to induce retrograde neuronal apoptosis in thalamus. In this animal model, unilateral ablation of the occipital cortex causes unequivocal apoptosis of corticopetal projection neurons in the dorsal lateral geniculate nucleus (LGN) by 7 days postlesion. We tested the hypothesis that p53 and Bax regulate this retrograde neuronal apoptosis. We found, by using immunocytochemistry, that p53 accumulates in nuclei of neurons destined to undergo apoptosis. By immunoblotting, p53 levels increase ( approximately 150% of control) in nuclear-enriched fractions of the ipsilateral LGN by 5 days after occipital cortex ablation. p53 is functionally activated in nuclear fractions of the ipsilateral LGN at 5 days postlesion, as shown by DNA binding assay (approximately fourfold increase) and by immunodetection of phosphorylated p53. The levels of procaspase-3 increase at 4 days postlesion, and caspase-3 is activated prominently at 5 days postlesion. To identify whether neuronal apoptosis in the adult brain is dependent on p53 and Bax, cortical ablations were done on p53 and bax null mice. Neuronal apoptosis in the dorsal LGN is significantly attenuated (approximately 34%) in p53(-/-) mice. In lesioned p53(+/+) mice, Bax immunostaining is enhanced in the ipsilateral dorsal LGN and Bax immunoreactivity accumulates at perinuclear locations in dorsal LGN neurons. The enhancement and redistribution of Bax immunostaining is attenuated in lesioned p53(-/-) mice. Neuronal apoptosis in the dorsal LGN is blocked completely in bax(-/-) mice. We conclude that neuronal apoptosis in the adult thalamus after cortical injury requires Bax and is modulated by p53.

Animals↗
PubMed2001

The cyclin-dependent kinase (CDK) inhibitor flavopiridol inhibits glycogen phosphorylase.

Flavopiridol has been shown to induce cell cycle arrest and apoptosis in various tumor cells in vitro and in vivo. Using immobilized flavopiridol, we identified glycogen phosphorylases (GP) from liver and brain as flavopiridol binding proteins from HeLa cell extract. Purified rabbit muscle GP also bound to the flavopiridol affinity column. GP is the rate-limiting enzyme in intracellular glycogen breakdown. Flavopiridol significantly inhibited the AMP-activated GP-b form of the purified rabbit muscle isoenzyme (IC50 of 1 microM at 0.8 mM AMP), but was less inhibitory to the active phosphorylated form of GP, GP-a (IC50 of 2.5 microM). The AMP-bound GP-a form was poorly inhibited by flavopiridol (40% at 10 microM). Increasing concentrations of the allosteric effector AMP resulted in a linear decrease in the GP-inhibitory activity of flavopiridol suggesting interference between flavopiridol and AMP. In contrast the GP inhibitor caffeine had no effect on the relative GP inhibition by flavopiridol, suggesting an additive effect of caffeine. Flavopiridol also inhibited the phosphorylase kinase-catalyzed phosphorylation of GP-b by inhibiting the kinase in vitro. Flavopiridol thus is able to interfere with both activating modifications of GP-b, AMP activation and phosphorylation. In A549 NSCLC cells flavopiridol treatment caused glycogen accumulation despite of an increase in GP activity, suggesting direct GP inhibition in vivo rather than inhibition of GP activation by phosphorylase kinase. These results suggest that the cyclin-dependent kinase inhibitor flavopiridol interferes with glycogen degradation, which may be responsible for flavopiridol's cytotoxicity and explain its resistance in some cell lines.

Adenosine Monophosphate↗
PubMed2001

Prognostic importance of isolated peritumoral lymphangiosis carcinomatosa in lymph-node-negative colorectal carcinoma.

BACKGROUND: The prognostic value of microinvasion of lymph vessels and lymph nodes has become increasingly important; there is a wide range in prognosis of patients with nodal-negative tumor stages after curative resection for colorectal cancer. AIM: Detection of the prognostic importance of isolated lymph-vessel invasion as a possible precursor of lymph-node metastasis in patients with nodal-negative tumor stages. PATIENTS/METHODS: Retrospective analysis of 894 patients with R0-resected colorectal cancer, uni- and multivariate analysis of tumorbiologic prognostic factors, immunohistochemical proof of tumor cells in negative lymph nodes (pN0) using the epithelial marker HEA-125 (human epithelial antigen). RESULTS: The incidence of lymph-vessel invasion (L) was 37.7% in total. A pN0,L1 status was found in 144 patients (16.1% of all analyzed patients). Comparing patients with pN0,L1 status to those with pN+,L0 status showed that both groups have similar rates of overall survival and tumor relapse. Lymph-node status, lymph-vessel invasion, depth of tumor infiltration (pT) stage, and age were detected as independent prognostic factors by multivariate analysis. After reanalysis of 54 cases primarily classified as 18.5% pN0,L1, microinvasion in lymph nodes was detected by immunohistochemistry. We found a higher rate of tumor relapse (approximately 20%) for those patients. In regard to the overall survival rate, however, there was no difference when compared to patients without immunohistochemical proof of microinvasion. CONCLUSION: Isolated lymph-vessel invasion in nodal-negative tumor stages and a lymph-node-positive tumor status have equivalent prognostic importance in colorectal cancer.

Aged↗
PubMed2001

Effect of drugs inhibiting spermidine biosynthesis and metabolism on the in vitro development of Plasmodium falciparum.

Treatment of Plasmodium falciparum with the potent inhibitor dicyclohexylamine completely arrests in vitro cell proliferation of the chloroquine-susceptible P. falciparum strain NF54 and the R strain, which shows less sensivity to chloroquine. The average inhibitory concentration (IC50) values determined for both strains revealed different inhibition profiles. The IC50 value for the chloroquine-sensitive NF54 strain was 97 microM and 501 microM for the R strain. Monitoring polyamine pools after treatment with dicyclohexylamine leads to a significant decrease in the intracellular spermidine content, which was nearly reversed by supplementation with spermidine. Since spermidine is an important precursor for the biosynthesis of hypusine and homospermidine in eukaryotes, we studied the developmental effect on both P. falciparum strains of 1,7-diaminoheptane as an inhibitor of deoxyhypusine synthase (EC 1.1.1.249) in mammalian cells, and agmatine as a moderate inhibitor of homospermidine synthase (EC 2.5.1.44). Inhibition profiles with 1,7-diaminoheptane resulted in an IC50 value of 466 microM for the NF54 strain and 319 microM for the R strain. Spermidine pools changed significantly. Inhibition with agmatine caused a strong decrease in parasitemia for the chloroquine-susceptible NF54 strain, with a determined IC50 value of 431 microM and an IC50 value of 340 microM for the less chloroquine-susceptible R strain. Spermidine was not detectable after inhibition. The uncommon triamine homospermidine occurred in both P. falciparum strains. To our knowledge this is the first evidence of homospermidine in P. falciparum. The use of specific inhibitors of spermidine metabolism might be a novel strategy for the design of new antimalarials, and suggests the occurrence of both enzymes in the parasite.

Agmatine↗
PubMed2001

A novel black-hooded mutant rat (ci3) with spontaneous circling behavior but normal auditory and vestibular functions.

Abnormal circling behavior in rodents is usually attributed to vestibular dysfunction. In rats, all circling mutants described previously have inner ear defects resulting in auditory and vestibular dysfunctions. Here, we describe a new mutant rat with abnormal spontaneous circling behavior but normal auditory and vestibular functions. The new circling mutant rat was discovered in progeny of an apparently normal black-hooded (BH) rat inbred line [BH.7A(LEW)/Won] and was termed ci3, because we recently found two other mutant circling rats (ci1 and ci2) in a Lewis (LEW) inbred rat strain. The ci3 mutant is characterized by circling behavior and locomotor hyperactivity, which occur in phases or bursts either spontaneously or in response to stress, e.g., when rats are transferred to a new environment. Video monitoring of undisturbed rats in their home cage during the light and dark periods showed that circling behavior is much more intense during the dark period, i.e., during the active phase of the animals. Most ci3 rats show a lateral preference in their rotational behavior, i.e., they either rotate to the left or to the right. Brainstem auditory evoked potential testing and different tests of vestibular function did not disclose any auditory or marked vestibular defects in ci3 rats. Furthermore, no morphological abnormalities were seen during histological examination of the cochlear and vestibular nuclei in the brainstem. Neurochemical determination of dopamine and dopamine metabolite levels in striatum, nucleus accumbens and substantia nigra showed that ci3 rats have a significant asymmetry in striatal dopamine in that dopamine levels were significantly lower in the hemisphere contralateral to the preferred direction of turning. Consistent with this finding, immunohistological examination of dopaminergic neurons in substantia nigra and ventral tegmental area yielded a significant laterality in the medial part of substantia nigra pars compacta with a lower density of tyrosine hydroxylase-positive neurons in the contralateral hemisphere of mutant circling rats, while no laterality was seen in unaffected rats of the background strain [BH.7A(LEW)/Won].Thus, the novel mutant ci3 rat exhibits several features which clearly differ from previously described circling rat or mouse mutants. The behavioral phenotype occurs in the absence of auditory or obvious vestibular defects and is most likely a consequence of lateralized abnormalities found in the nigrostriatal circuit. Apart from the use of ci3 rats for studying the functional lateralization of brain functions, the ci3 mutant may serve as a new model for movement disorders with abnormal lateralization.

Animals↗