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J Kroll

Publications and source records attributed to J Kroll.

At least 37 records · Page 2Linked to original sources

Clinical experience with heart transplantation in infants.

OBJECTIVE: Orthotopic heart transplantation has become an accepted therapeutic concept for adult patients with endstage heart disease. In newborns and infants this procedure is still a matter of discussion because of unknown long-term results and the lack of donor organs. METHODS: Since March 1988 we have performed 40 orthotopic heart transplantation in 39 infants who were from 1 to 280 days of age. Indications for transplantation included hypoplastic left-heart syndrome (n = 28), dilative cardiomyopathy (n = 4), endocardial fibroelastosis (n = 4) and other complex structural anomalies (n = 3). The mean waiting period for transplantation was 53 days. A donor-recipient weight ratio up to 4.0 was accepted. Profound hypothermic circulatory arrest was used for graft implantation in all those patients who required extensive aortic arch reconstruction (71%). The initial immunomodulation was based on Cyclosporine, Azathioprine and Prednisolone. Patients who underwent transplantation during the first 6 weeks of life received a chronic single-drug therapy with Cyclosporine after 1 year. RESULTS: There were six peri-operative deaths caused by drug-resistant right-heart failure in three cases, humoral rejection (n = 1), CMV infection (n = 1) and multi organ failure (n = 1). One infant died late, due to rejection. The actuarial survival rate for the entire group is now 82%. There is a remarkable influence of increasing experience. Whereas six of 15 infants who had heart transplantation between 1988 and 1993 died early post-operatively (survival rate: 60%), only one late death occurred among 24 recipients in the period from 1994 to April 1997 (survival rate: 96%). Episodes of rejection occurred once or several times in about half of the patients in this series (48%). All surviving children are living at home in excellent condition. CONCLUSIONS: Heart transplantation during early infancy is a rational and durable therapy for heart diseases with irreversible myocardial failure or severe structural anomalies. The intermediate-term results have been encouraging in many centers, but more data must be accumulated to determine the sequelae of chronic immunosuppression. The lack of donor organs remains one of the major problems in pediatric heart transplantation.

Body Height↗

[Frequency, distribution and prognostic relevance of p53 mutations in soft tissue sarcomas].

Soft tissue sarcomas although rarely occurring (about 1% of malignant tumors), are because of their histo-morphological diversity and often similar appearance to tumor-like lesions difficult to characterize and estimate in their tumor biological behaviour. Analysis of molecular characteristics as alterations in tumor-suppressor and oncogenes may allow insight in STS genesis. We have chosen the in carcinomas well, but in STS not comprehensively investigated tumor-suppressor gene p53 for mutational analysis. In 16 out of 146 STS patients we could identify p53-mutations. In a multivariate Cox-regression analysis prognosis was correlated with the p53-mutation type. However, only patients with non-frameshift mutations possessed a poorer prognosis (RR = 2.42; p = 0.014) in comparison to patients without mutations, but frameshift-mutations didn't seem to affect prognosis negatively. Compiling our results and those of the literature an overall frequency of 16.3% of p53-mutations in STS, with various frequencies in different entities is detectable. STS specific hotspots are not recognizable. Rather mutational hotspots in codons 175, 245, 248 and 273 well known from studies in carcinomas are also apparent in STS. Summarizing, we want to state that the occurrence of p53-mutations (non-frameshift mutations) is of prognostic importance in STS. Combination of histo-pathological, clinical and molecular characteristics may allow to distinguish in future different groups of patients for an individual treatment.

Codon↗

The vascular endothelial growth factor receptor KDR activates multiple signal transduction pathways in porcine aortic endothelial cells.

Vascular endothelial growth factor A (here referred to as VEGF) is an endothelium-specific growth factor that binds to two distinct receptor tyrosine kinases, designated Flt-1 and KDR/Flk-1. VEGF stimulates autophosphorylation of both receptors, but little is known about their signal transduction properties. In this study, we used porcine aortic endothelial (PAE) cells overexpressing KDR (PAE/KDR) to evaluate the interaction of KDR with intracellular proteins and compared them with Flt-1-expressing PAE cells (PAE/Flt-1). VEGF-induced stimulation of KDR results in the association and phosphorylation of the 46-, 52-, and 66-kDa isoforms of Shc and the induction of Shc-Grb2 complex formation. In a similar fashion, KDR associates with Grb2 and Nck in a ligand-dependent fashion, suggesting Shc, Grb2, and Nck as potential candidates involved in the regulation of endothelial function. Another strong candidate is mitogen-activated protein (MAP) kinase, which is strongly activated in response to VEGF stimulation as demonstrated by phosphorylation of the specific substrate myelin basic protein. Inhibition of MAP kinase activation by PD98059, a specific MAP kinase kinase inhibitor, results in inhibition of VEGF-induced proliferation of PAE/KDR cells. In contrast, VEGF-induced stimulation of Flt-1 does not activate MAP kinase in PAE/Flt-1 cells. In this study we provide the first two examples of molecules potentially capable of functionally counteracting the endothelial response to VEGF, namely SHP-1 and SHP-2. These two SH2 protein-tyrosine phosphatases physically associate with KDR secondary to VEGF stimulation, raising the interesting possibility that both molecules participate in the generation and/or modulation of VEGF-induced signals. Taken together, our results substantially broaden the spectrum of KDR-associating molecules, indicating that endothelial function and angiogenesis are regulated by a diverse network of signal transduction cascades.

Animals↗

An educational intervention as decision support for menopausal women.

The purpose of this study was to develop and test a decision support intervention (DSI) to assist women to make and act on informed decisions that are consistent with their values in the area of menopause and hormone replacement therapy (HRT). Mode and intensity of intervention were tested in midlife women (N = 248), randomly assigned to one of three intervention formats: written information only, guided discussion, or personalized decision exercise. Data were collected over 12 months. Knowledge, decisional conflict, satisfaction with health care provider, and self-efficacy improved following intervention and were maintained for 12 months for all groups. Women's adherence to their own plans over 12 months was 59% (exercise), 76% (calcium intake), and 89% (HRT). Carefully written information is effective in promoting knowledge, adherence, and satisfaction among well-educated, interested women. It was concluded that women can understand complex information, including tradeoffs regarding treatment options. Women will adhere to their own plans, suggesting that consumer rather than provider plans may be the more appropriate gold standard for measuring adherence.

Adult↗

Frequent occurrence of p53 mutations in rhabdomyosarcoma and leiomyosarcoma, but not in fibrosarcoma and malignant neural tumors.

We have analyzed soft-tissue sarcomas (STS) molecularly for mutations in the tumor-suppressor gene p53 and immunohisto-chemically for expression of p53 and mdm2 proteins. In this study, tumor samples from 3 groups of soft-tissue sarcomas, i.e., fibrosarcomas, myogenic sarcomas and malignant neural tumors (MNT), were investigated. The methods applied encompass immunohistochemistry on 198 tumor samples using p53 antibodies (DO-1 and DO-7) and an mdm2 antibody (IF-2). Out of these, 100 samples were subjected to non-radioactive PCR-SSCP-sequencing analysis. Immunohistochemical detection rate for p53 (range of 57% to 67%) and for mdm2 proteins (range of 19 to 44%) was similar in all 3 groups. In higher tumor grades, an increased rate of immunopositivity was found for p53 but not for mdm2. Investigation of p53 mutational status revealed 6 mutations in myogenic sarcomas but none in malignant neural tumors or fibrosarcomas, suggesting different roles of p53 in the 3 STS groups. Interestingly, a G-->A transition in codon 245 (a CpG site) was found in 3 myogenic sarcomas. Our results and those of others suggest p53 codon 245 as a mutational hotspot in sarcomas, as recognized in carcinomas.

Base Sequence↗

Some aspects of reactions of benzyl isothiocyanate with bovine sarcoplasmic proteins.

Benzyl-ITC (benzyl isothiocyanate) reacts preferentially with amino groups and sulfhydryl side chains of bovine sarcoplasmic proteins to form thiourea and dithiocarbamate derivatives, generally resulting in a decrease in solubility of the derivatives along a wide pH range. Under these conditions, it was also possible to show that secondary amine side chains, as found in tryptophan, also react with benzyl-ITC. A quenching of tryptophan fluorescence intensity after interaction with benzyl-ITC was also observed. Polyacrylamide gel electrophoresis (PAGE) experiments in the presence of urea indicated changes in electrophoretical mobility and in composition of subfractions. Changes in surface hydrophobicity and composition as determined by the ANS (8-anilinonaphthalene-1-sulfonate) method and RP-HPLC were also observed. Polymerisation of protein molecules after reaction with benzyl-ITC was documented using the SDS-PAGE technique. These investigations showed that a group of subfractions belonging mainly to glycolytic enzymes and associated proteins with molecular weight between 38-70 kDa was highly reactive.

Animals↗

[Cerebral oximetry by infrared spectroscopy in comparison with continuous measurement of oxygen saturation of the jugular vein bulb in interventions of the internal carotid artery].

OBJECTIVE: Monitoring the central nervous system during carotid endarterectomy plays an important role in detection of cerebral ischemia. With optical spectroscopy in the near-infrared light range it is now possible to measure regional cerebral oxygen saturation (rSO2) noninvasively. Numerous studies emphasize the importance of cerebral oxygen balance rather than absolute values of cerebral blood flow or metabolic rate. In this study data from oxygen saturation measured in the jugular bulb (SJO2) were compared to rSO2. METHODS: 10 patients undergoing elective carotid end-arterectomy were enrolled after written informed consent and approval by the local ethics committee. rSO2 data were measured by cerebral spectroscopy (INVOS 3100, Somanetics, Michigan/USA). To avoid lesions of the internal carotid artery, a 4-F oxymetry catheter (OPTICATH, Abbot GmbH, Wiesbaden) was placed in the jugular bulb by retrograde approach after preparation by the surgeon. Anaesthesia and mechanical ventilation were standardised. RESULTS: After cross-clamping of the internal carotid artery rSO2 significantly decreased (60.5 +/- 3.5%) compared to baseline (66.0 +/- 1.4%). After declamping rSO2 increased significantly (63.0 +/- 4.2%) and was close to baseline at the end of operation (65.0 +/- 2.8%). The SJO2 time course showed good correlation compared to rSO2 data (r = 0.85). After cross-clamping SJO2 decreased significantly (51.5 +/- 6.3%) in comparison to baseline (59.5 +/- 4.9%). Declamping increased SJO2 to 59.5 +/- 6.3%. No changes in latencies or amplitudes of SEP were observed throughout the operation. CONCLUSIONS: Noninvasive cerebral optical spectroscopy is a useful tool to determine the brain tissue oxygenation. The positive correlation to jugular bulb oxygen saturation is somewhat unexpected as rSO2 evaluates regional while SJO2 measures global oxygen content. However our results suggests that both methods are able to detect episodes of cerebral ischemia during carotid endarterectomy. The interpretation of the changes of cerebral oxygen saturation with respect to neurological outcome warrants further studies.

Aged↗

Toxicological evaluation of rapeseed products in a subacute feeding study in rats.

Groups of 15 male rats were fed ad libitum for 4 weeks standard diet containing 0, 2.5, 5 or 10% rapeseed protein isolate (RPI), 2.5, 5 or 10% rapeseed extraction residue (RER) or 10% casein. Body weight gain and food intake were recorded weekly. Clinical chemistry analyses, haematology, urinalysis, organ weights and histology were performed terminally. Serum alanine aminotransferase was decreased by RPI, RER and casein, while serum albumin only increased in rats fed RER. Microscopic examinations revealed abnormalities in liver and kidneys of animals at the 10% RPI, RER and casein levels. The absolute liver weights showed increases in the 5 and 10% RER groups and in the 10% RPI group. The relative kidney weights were reduced at all RER levels and in the 2.5% RPI group. Antithyroid activity of the rapeseed products were not noted.

Alanine Transaminase↗

Capturing and clustering women's judgment policies: the case of hormonal therapy for menopause.

Two hundred sixty-five women estimated the likelihood that they would take estrogen plus progestin to alleviate menopausal symptoms when faced with hypothetical cases varying in degree of hot flashes and risk of osteoporosis and cancer. Clustering of their judgment policies revealed four groups of women with respect to their approach to this decision. These groups of women were significantly different from each other on educational level, perceived experience of stress, and attitudes toward menopause and use of medications. Willingness to take hormonal therapy across all cases was related to attitudes about, and knowledge of, menstruation, perceived stress, mother's experience with menstrual problems, severity of symptoms, and use of vitamins. While there have been previous attempts to cluster rater policies, the current study represents a novel attempt to understand the differences between people who appear to have different policies about a decision problem, in this case, whether or not to take hormone therapy to counter menopausal symptoms.

Attitude↗

Women's use of information regarding hormone replacement therapy.

For perimenopausal women, an important decision is whether or not to use hormone replacement therapy (HRT). The decision is complex because HRT involves judgment in weighing gains and losses related to physiological risk. Gains involve relief of hot flashes and prevention of osteoporosis; losses include cancer mortality and side effects of medication. A policy-capturing study of 283 perimenopausal women showed that the factor of most frequent concern was relief of hot flashes. Cluster analyses identified four major groups. Group 4 had an n of 9 and the lowest R2, making interpretation of data questionable. The largest group responded to hot flashes alone; the second to hot flashes and osteoporosis; and the third to hot flashes, somewhat to osteoporosis, but also to side effects of estrogen/progestin therapy. Results indicate nursing interventions should anticipate differences in women's concerns and tailor counseling appropriately.

Climacteric↗

Obsession or worry?

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Anxiety Disorders↗

Medication compliance, antidepressant blood levels, and side effects in Southeast Asian patients.

A study of medication compliance, side effects, and clinical change with the use of antidepressants in 32 Southeast Asian refugee patients seen at an urban mental health center is reported. Patients met criteria for either major depressive episode, posttraumatic stress disorder, or both. Only five of the 32 patients who stated that they were taking their medications regularly had antidepressant blood levels in the therapeutic range. Another 10 patients had subtherapeutic levels and the remaining 17 had undetectable blood levels. Patients with therapeutic blood levels had fewer side effects (p = 0.049) than patients with undetectable blood levels. Blood levels tended (p = 0.070) to be correlated with clinical improvement. The authors discuss cultural attitudes of Southeast Asian refugee patients toward medication use and side effects that appear to influence medication compliance.

Adult↗