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Biomedical subjects

N Klein

Publications and source records attributed to N Klein.

At least 55 records · Page 3Linked to original sources
PubMed2000

Differential binding of mannose-binding lectin to respiratory pathogens in cystic fibrosis.

We have found that mannose-binding lectin binds to Burkholderia cepacia, an important pathogen in patients with cystic fibrosis, and leads to complement activation, but that this is not the case for Pseudomonas aeruginosa, the more common colonising organism in this disease. We suggest that patients with cystic fibrosis with mannose-binding-lectin deficiency will be at particular risk of B cepacia colonisation.

Burkholderia cepacia↗
PubMed2000

[Alcohol concentration in the coronary sinus after transarterial ablation of septal hypertrophy in hypertrophic obstructive cardiomyopathy].

BACKGROUND AND OBJECTIVE: The size of the resulting myocardial necrosis varies after percutaneous transarterial ablation (PTA) of hypertrophied septum in patients with hypertrophic obstructive cardiomyopathy (HOCM). It was the aim of this study to discover whether the alcohol concentration in coronary sinus (CS) blood is a useful and appropriate parameter and what conclusions can be drawn from it. PATIENTS AND METHODS: PTA was done in four patients (two women and two men, aged 30-53 years) with HOCM. Before the intervention the gradient across the left ventricular outflow tract ranged form 20 to 80 mmHg, postextrasystolic it ranged from 40 to 180 mmHg. 1 x 2 ml ethanol was injected into the first septal branch in 3 patients, 2 x 2 ml in one. The alcohol concentration in coronary sinus blood was measured every 30 sec for up to 5 min before and after ablation. The amounts were compared with the size of the akinetic area in the echocardiogram and the maximal value of creatine kinase, as a measure of the size of myocardial necrosis. RESULTS: The left ventricular outflow gradient was reduced in all patients, to 0-30 mmHg and postextrasystolic to 30-90 mmHg. A pacemaker had to be implanted in one patient who developed a 3 degrees AV block. The alcohol concentration in coronary sinus blood ranged from maximally 1.53 and 0.23 per thousand after 30 sec and then fell to 0.56-0.12 per thousand after 5 min. The patient with the highest CS alcohol concentration also had the highest maximal value for creatine kinase (68 mumol/l) and the largest akinetic area in the echocardiogram. CONCLUSION: The extent of myocardial necrosis can probably be estimated from the CS blood concentration of alcohol after alcohol ablation. If, after the first injection, high alcohol concentrations are measured, further alcohol injections are not indicated.

Adult↗
PubMed2000

Immune repopulation after HAART in previously untreated HIV-1-infected children. Paediatric European Network for Treatment of AIDS (PENTA) Steering Committee.

In 25 vertically HIV-infected children receiving highly-active antiretroviral therapy, a 3-log10 reduction in plasma HIV RNA load was maintained for 1 year and was associated with a doubling of the CD4-cell percentage. Most (75%) new CD4 cells carried the CD45RA marker of naive cells and there was only a small rise in memory cells (CD45RO). This pattern of immune restoration differs from adults, and may be due to the presence of a functioning thymus in children.

Anti-HIV Agents↗
PubMed2000

Immunomodulatory effects of breast milk oligosaccharides.

Breast milk oligosaccharides are excreted in urine in amounts that suggest that they may exist in the circulation at levels compatible with a physiological function. Some oligosaccharides have structural similarity to cellular adhesion molecules and may influence adhesion of cells in breast fed infants. In this study, breast milk oligosaccharides were purified and incubated in assays of cell adhesion. They were found to inhibit neutrophil adhesion to stimulated vascular endothelial cells in a dose dependent fashion. In contrast they enhanced platelet-neutrophil complex formation. These results indicate that breast milk oligosaccharides may play a physiological role in modulating cellular adhesion in vivo.

Absorption↗
PubMed2000

Is leukocytosis a predictor of mortality in severe pertussis infection?

Bordetella pertussis causing severe respiratory failure in infants that is unresponsive to treatment is well described. Pulmonary hypertension is a prominent feature of such cases. In this series of 13 critically ill infants with B. pertussis, hyperleukocytosis ( > 100 x 10(9)/l) was an independent predictor of death. We suggest that such extreme leukocytosis may contribute to disease severity via the formation of aggregates in the pulmonary vasculature.

Blood Gas Analysis↗
PubMed2000

[CO2 laser in ophthalmology].

BACKGROUND: Baker et al. used a CO2 laser for blepharoplasty for the first time. The ultra-pulse CO2 laser provides a sophisticated instrument that makes more application alternatives possible in ophthalmology. PATIENTS AND METHODS: From March 1997 to February 1998 surgical operations were performed in the eye clinics in Hagen and Darmstadt using the CO2 laser: 145 eyelid operations and 8 others (enucleation, evisceration, oral mucosa plastic surgery, secondary hydroxyapatite implantation, squint operation). In 34 patients in a total of 64 operations, after an average follow-up period of 7 (4-11) months, an examination was carried out. RESULTS: There were serious complications in only one case. Three weeks after transconjunctival fat resection and resurfacing, one patient developed an inflammatory reaction with resulting ectropion on both sides. During steroid therapy the left lower lid flattened, but on the right side a slight ectropion remained. CONCLUSION: The CO2 laser proved to be a very useful instrument for bloodless tissue-protective surgery without conspicuous scar formation.

Blepharoplasty↗
PubMed2000

[Catheter ablation of supraventricular tachyarrhythmias].

The term "supraventricular tachyarrhythmia" summarizes electrophysiologically different arrhythmias. After detection of the mechanism of the present arrhythmia, the weak part of the reentrant circuit has to be identified using different mapping techniques. The catheter ablation is widely used as focal ablation (sinus tachycardia, ectopic atrial tachycardia, focal atrial fibrillation) or for interruption of conducting pathways (accessory pathways, AV nodal reentrant tachycardia). A single ablation line should be created in isthmus-dependent atrial flutter or in incisional tachycardias, which is less used now-a-days. Multiple ablation lines are needed for ablation of atrial fibrillation, which is a method investigated in arrhythmia centers only. Some arrhythmias are less well understood, not localizable and therefore not curatively treated with ablation techniques. Newer three-dimensional mapping methods may help in this situation. The challenge at the present time is the catheter ablation of atrial fibrillation.

Catheter Ablation↗
PubMed2000

Isolated cutaneous response to granulocyte-monocyte colony stimulating factor in fatal idiopathic disseminated Bacillus-Calmette-Guerin infection.

UNLABELLED: Severe disseminated Bacillus-Calmette-Guerin (BCG) infection is very rare and has been regarded as idiopathic when no immunodeficiency is present. This entity seems to be due to several new types of inherited abnormalities in the pathways important in defence against Mycobacteria. Although improvement with interferon-gamma (IFN-gamma) has been reported in some patients, to our knowledge there are no reports on the effect of other cytokines in the treatment of these patients. We report here the clinical response to IFN-gamma and granulocyte-monocyte colony stimulating factor (GM-CSF) treatment in a patient with idiopathic disseminated BCG infection who failed to respond to multiple antimycobacterial agents. The patient showed partial and transitory response to IFN-gamma, however, GM-CSF treatment led to rapid improvement of skin lesions within 2 weeks without any effect on the progression of the disease in the other organ systems. CONCLUSION: The response of idiopathic disseminated Bacillus-Calmette-Guerin infection to granulocyte-monocyte colony stimulating factor treatment was limited to cutaneous lesions. Granulocyte-monocyte colony stimulating factor may have acted to promote wound healing or the levels of this factor achieved in other affected organs may have been inadequate.

BCG Vaccine↗
PubMed2000

Relationship between in vivo drug exposure of the tumor interstitium and inhibition of tumor cell growth in vitro: a study in breast cancer patients.

A novel approach is described to simulate effect site pharmacodynamics of anticancer drugs. This approach is based on (i) the in vivo measurement of unbound, interstitial drug pharmacokinetics (PK) in solid tumor lesions in patients and (ii) a subsequent pharmacodynamic (PD) simulation of the time versus drug concentration profile in an in vitro setting. For this purpose, breast cancer cells (MCF-7) were exposed in vitro to the time versus interstitial tumor concentration profiles of 5-fluorouracil (5-FU) and methotrexate (MTX) from primary breast cancer lesions in patients. This led to a maximal reduction in the viable cell count of 69% on day 4, and of 71% on day 7 for 5-FU and MTX, respectively. This effect was dependent on the initial cell count and was characterized by a high interindividual variability. For 5-FU there was a significant correlation between the maximum antitumor effect and the intratumoral AUC (r = -0.82, p = 0.0005), whereas no correlation could be shown for MTX (r = 0.05, p = 0.88). We conclude, that the in-vivo-PK / in-vitro-PD model presented in this study may provide a rational approach for describing and predicting pharmacodynamics of cytotoxic drugs at the target site. Data derived from this approach support the concept that tumor penetration of 5-FU may be a response-limiting event, while the response to MTX may be determined by events beyond interstitial fluid kinetics.

Antimetabolites, Antineoplastic↗
PubMed2000

Gram-negative bacteria induce proinflammatory cytokine production by monocytes in the absence of lipopolysaccharide (LPS).

Tumour necrosis factor-alpha (TNF-alpha), IL-1alpha and IL-6 production by human monocytes in response to a clinical strain of the Gram-negative encapsulated bacteria Neisseria meningitidis and an isogenic lpxA- strain deficient in LPS was investigated. Wild-type N. meningitidis at concentrations between 105 and 108 organisms/ml and purified LPS induced proinflammatory cytokine production. High levels of these cytokines were also produced in response to the lpxA- strain at 107 and 108 organisms/ml. The specific LPS antagonist bactericidal/permeability-increasing protein (rBPI21) inhibited cytokine production induced by LPS and wild-type bacteria at 105 organisms/ml but not at higher concentrations, and not by LPS-deficient bacteria at any concentration. These data show that proinflammatory cytokine production by monocytes in response to N. meningitidis does not require the presence of LPS. Therapeutic strategies designed to block LPS alone may not therefore be sufficient for interrupting the inflammatory response in severe meningococcal disease.

Acyltransferases↗
PubMed2000

Oligosaccharides in human milk: structural, functional, and metabolic aspects.

Research on human milk oligosaccharides (HMOs) has received much attention in recent years. However, it started about a century ago with the observation that oligosaccharides might be growth factors for a so-called bifidus flora in breast-fed infants and extends to the recent finding of cell adhesion molecules in human milk. The latter are involved in inflammatory events recognizing carbohydrate sequences that also can be found in human milk. The similarities between epithelial cell surface carbohydrates and oligosaccharides in human milk strengthen the idea that specific interactions of those oligosaccharides with pathogenic microorganisms do occur preventing the attachment of microbes to epithelial cells. HMOs may act as soluble receptors for different pathogens, thus increasing the resistance of breast-fed infants. However, we need to know more about the metabolism of oligosaccharides in the gastrointestinal tract. How far are oligosaccharides degraded by intestinal enzymes and does oligosaccharide processing (e.g. degradation, synthesis, and elongation of core structures) occur in intestinal epithelial cells? Further research on HMOs is certainly needed to increase our knowledge of infant nutrition as it is affected by complex oligosaccharides.

Bifidobacterium↗
PubMed2000

School-age consequences of birth weight less than 750 g: a review and update.

Recent advances in perinatal care have led to the survival of increasing numbers of children born at the lower limits of viability. Children with very low birth weight (LBW; less than 1,500 g, 3 lb 5 oz) have been studied extensively. Findings document poorer outcomes relative to normal birth weight term-born controls in neurologic and health status, cognitive-neuropsychological skills, school performance, academic achievement, and behavior. This report reviews current knowledge regarding LBW children, with special emphasis on outcomes for children with birth weight less than 750 g (1 lb 10 oz). Results from an ongoing longitudinal study suggest a gradient of sequelae, with poorer outcomes in less than 750 g birth weight children compared to both 750 g to 1,499 g birth weight children and term-born controls. Children with less than 750 g birth weight fail to catch up with their peers over time and may even be at risk for age-related increases in sequelae. Outcomes are highly variable but related to neonatal medical complications of prematurity and social risk factors. Further research is needed to understand the etiology and neuropathological basis of sequelae, the long-term developmental implications of LBW, and treatment needs.

Child↗
PubMed2000

Functional limitations and special health care needs of 10- to 14-year-old children weighing less than 750 grams at birth.

OBJECTIVE: To examine the health status, functioning, and special health care needs of children 10 to 14 years old weighing <750 g at birth. METHODS: We compared outcomes of a regional cohort of 59 children born from 1982 through 1986 weighing <750 g at birth (mean: 665 g; gestational age: 26 weeks) to matched groups of 54 children weighing 750 to 1499 g at birth and 49 children born at term. Assessments of limitations in functioning, compensatory dependence and needs for services above routine, at a mean age of 11 years, were based on responses to maternal questionnaires. Rates of these outcomes were compared between groups using logistic regression analyses that controlled for gender and social risk. RESULTS: Children weighing <750 g at birth had significantly higher rates of functional limitations, greater compensatory dependence, and need for services above routine than the other 2 groups. Compared with children born at term, the odds ratio for mental or emotional delay was 4.7 (95% confidence interval [CI]: 2.0-11.0), for restrictions in activity, 5.1 (CI: 1.6-16.3) and for blindness or difficulty seeing 3.9 (CI:1.3-11.4). With the exception of 3% of children who were severely impaired, the only compensatory aid that differentiated the children weighing <750 g at birth from the children born at term was the greater need for glasses (odds ratio [OR]: 2.8 [CI: 1.3-6.3]). Increased services above routine included special education (OR: 5.0 [CI: 2.1-11.7]), counseling (OR: 4.8 [CI: 1.0-23.1]) and special arrangements in school (OR: 9.5 [C.I. 2.1-43. 6]). CONCLUSION: Parents and educators need to be informed of the potential for disability and special health care needs of children weighing <750 g at birth.

Activities of Daily Living↗
PubMed1999

Dual role for noradrenergic innervation of lymphoid tissue and arthritic joints in adjuvant-induced arthritis.

The role of noradrenergic innervation in the disease outcome of adjuvant-induced arthritis (AA) has been examined following (1) systemic administration of guanethidine and (2) local application of 6-hydroxydopamine (6-OHDA) into the lymph nodes that drain the hind limbs (DLN). Sympathetic denervation by these different neurotoxins produced directionally opposite effects on disease outcome. These conflicting findings could be explained from differential denervation of sympathetic nerves in key target tissues that result from different routes of neurotoxin administration. Alternatively, these conflicting data could be due to differences in the mechanisms by which guanethidine and 6-OHDA destroy sympathetic nerve terminals. In this study, we compared disease outcome in AA following systemic and local DLN application of 6-OHDA to determine whether the route of administration is important to the development and progression of AA. Bilateral local DLN application of 6-OHDA or vehicle was performed 1 day before injection of Freund's complete adjuvant (CFA) to induce arthritis. For systemic denervation, 6-OHDA or vehicle was given by ip injections on days 1, 3, and 5 prior to CFA challenge and then once a week. Local DLN application of 6-OHDA resulted in significant increases in dorsoplantar width in arthritic rats by 27 days following CFA treatment compared to those of non-denervated arthritic rats. In contrast, systemic denervation in arthritic rats significantly decreased dorsoplantar widths 27 days after CFA treatment compared to those in sympathetically intact arthritic animals. X-ray analysis confirmed these findings. Further, local DLN application of 6-OHDA exacerbated the disease regardless of whether the neurotoxin was administered prior to immunization with CFA or closer to the time of disease onset. Our findings indicate that the route of 6-OHDA administration for denervation of sympathetic innervation is an important parameter in determining disease outcome, presumably due to differential sympathetic denervation of target tissues that are involved in disease development and progression. 6-OHDA administration into local DLN denervated these lymph nodes, but spared sympathetic innervation of the hind limbs, a pattern of sympathetic denervation that resulted in disease exacerbation. In contrast, systemic 6-OHDA administration which denervated both the arthritic joints and the secondary lymphoid organs attenuated the severity of AA. This study supports a dual role for NA innervation in modulating the severity of AA by innervation of the arthritic joints and lymphoid organs.

Animals↗
PubMed1999

Free radical formation in infants: the effect of critical illness, parenteral nutrition, and enteral feeding.

BACKGROUND/PURPOSE: An increase in free radical activity has been observed in patients suffering from a variety of illnesses and has been correlated with disease severity. Free radical production is increased by the administration of total parenteral nutrition (TPN) and may be linked to its adverse effects. Some of the complications of TPN can be ameliorated by partial enteral feeding. The aim of this study was to investigate free radical activity during critical illness and during the administration of parenteral nutrition. METHODS: Three groups of surgical infants were studied: (1) control infants (n = 8) before minor surgery, (2) stable infants on the ward recovering from a major operation (n = 24), (3) critically ill infants in the neonatal intensive care unit (NICU, n = 28). Fourteen patients in the ward and 17 patients in NICU were receiving parenteral nutrition. Of the 31 patients on TPN, 9 were also receiving minimal enteral feeding (3% to 24% of total calorie intake). Plasma malondialdehyde (MDA), an index of free radical activity, was measured in all 60 infants. The Paediatric Risk of Mortality (PRISM) score was obtained on NICU patients. The cytokines tumor necrosis factor (TNF-alpha) and interleukin 6 (IL-6) were measured in 25 patients. RESULTS: Plasma MDA was significantly higher in (1) the stable patients on the ward compared with control patients (P < .001) and (2) patients in NICU compared with stable patients in the ward (P < .001). Parenteral nutrition was associated with higher levels of plasma MDA both in stable patients in the ward and critically ill infants in NICU. There was no correlation between the PRISM score and MDA. In patients not receiving TPN there is a correlation between MDA and TNF-alpha (r = 0.54, P = .02) and between MDA and IL-6 (r = 0.74, P = .001). The level of free radical activity in patients on TPN is not changed by partial enteral feeding. CONCLUSIONS: Critical illness causes a rise in free radical production. Parenteral nutrition causes a significant elevation in free radical activity in both stable infants in the ward and critically ill infants in NICU. The addition of minimal enteral feeding to parenteral nutrition does not reduce free radical activity. We hypothesize that the parenteral nutrition solution directly initiates free radical production.

Analysis of Variance↗
PubMed1999

The MYC dualism in growth and death.

Over-expression of the transcription factor c-Myc immortalizes primary cells and transforms in co-operation with activated ras. Therefore, c-myc is considered a proto-oncogene. Since its discovery c-Myc has been shown to render cells growth factor independent, accelerates passage through G1 of the cell cycle, inhibits differentiation and elicits apoptosis. Whereas the effects on immortalization, proliferation and inhibition of differentiation are in conceivable accordance with gain of function, as it is defined for a proto-oncogene, its pro-apoptotic activity disables a straight forward explanation of the physiological role of c-Myc and suggests a highly complex contribution during development. The recent accomplishments in c-Myc research shed some light on the difficile regulatory network which keeps check on c-Myc activity such as by binding to proteins some of which are transcription factors for non-c-Myc targets. Moreover, it was shown that genes are targeted by c-Myc depending on the sequence of flanking regions adjacent to the E-box or in dependence on the availability of binding partners which is most probably specific to the cellular context. Cdc25A and ornithine decarboxylase, both described to be c-Myc targets, have been brought forward as downstream effectors in the induction of proliferation under serum rich conditions, or in the induction of apoptosis when serum factors are limited. These genes seem to be regulated by c-Myc in a cell type-specific manner. H-ferritin, IRP2 and telomerase are the most recently discovered direct targets of c-Myc. The regulation of H-ferritin and IRP2 might explain the potential of c-Myc to promote proliferation and the regulation of telomerase could be responsible for the immortalizing properties of c-Myc. In the future, H-ferritin and telomerase have to be analyzed whether or not these genes are also Myc targets in other cell systems. Although the intense research efforts regarding the function of c-Myc last already two decades the role of this gene is still enigmatic.

Animals↗
PubMed1999

Inhibin-B as a test of ovarian reserve for infertile women.

The objective of the study was to compare a standard clomiphene citrate challenge test with inhibin-B serum concentrations also obtained on cycle days 3 and 10 as a negative predictor of pregnancy in a group of 106 women at risk for compromised ovarian function. Mean duration of follow-up was 8.25 months in 95 patients with 30 pregnancies recorded (plus one biochemical). Inhibin-B concentrations on cycle days 3 and 10 were correlated only with each other and not with serum oestradiol, follicle stimulating hormone (FSH) and/or pregnancy rates. Pregnancy occurred in 34.5% (10/29) of all patients with inhibin-B values >/=45 pg/ml on cycle day 3 and in 31.8% (21/66) of those with values <45 pg/ml. For FSH >11 mIU/ml on either day, pregnancy rate was 13.6% versus 38.4% for FSH of </=9 mIU/ml (P = 0.03). This study reconfirmed the usefulness of a clomiphene citrate challenge test as an indication of ovarian reserve but failed to find clinical value for inhibin-B testing.

Adult↗