Biomedical subjects
Publications and source records attributed to J Klein.
The authors discuss the technique of identification and biopsy of sentinel lymph nodes in tumors of the upper gastrointestinal tract. They describe difficulties and problems of the technique, in which the identified sentinel lymph node is obtained mainly employing endoscopical and minimally invasive techniques.
Using surface force balance measurements we have established that polystyrene chains bearing three zwitterionic groups have a higher end-group sticking energy than equivalent chains bearing a single zwitterionic group. In a good solvent, polystyrene chains end-functionalized with three zwitterionic groups form brushes of a higher surface coverage than those bearing a single zwitterion. The increase in surface coverage is slow compared with the initial formation of the brush. Measurements of the refractive index allow us to directly quantify the variation of surface coverage, permitting comparison with models for the kinetics of brush formation based on scaling theory and an analytical self-consistent field. We find qualitative support for associating the kinetic barrier with the energy required for an incoming chain to stretch as it penetrates the existing brush.
BACKGROUND: The open lung concept (OLC) is a method of ventilation intended to maintain end-expiratory lung volume by increased airway pressure. Since this could increase right ventricular afterload, we studied the effect of this method on right ventricular afterload in patients after cardiac surgery. METHODS: We studied 24 stable patients after coronary artery surgery and/or valve surgery with cardiopulmonary bypass. Patients were randomly assigned to OLC or conventional mechanical ventilation (CMV). In the OLC group, recruitment manoeuvres were applied until Pa(o(2))/FI(O(2)) was greater than 50 kPa (reflecting an open lung). This value was maintained by sufficient positive airway pressure. In the CMV group, volume-controlled ventilation was used with a PEEP of 5 cm H(2)O. Cardiac index, right ventricular preload, contractility and afterload were measured with a pulmonary artery thermodilution catheter during the 3-h observation period. Blood gases were monitored continuously. RESULTS: To achieve Pa(O(2))/Fl(O(2)) > 50 kPa, 5.3 (3) (mean, SD) recruitment attempts were performed with a peak pressure of 45.5 (2) cm H(2)O. To keep the lung open, PEEP of 17.0 (3) cm H(2)O was required. Compared with baseline, pulmonary vascular resistance and right ventricular ejection fraction did not change significantly during the observation period in either group. CONCLUSION: No evidence was found that ventilation according to the OLC affects right ventricular afterload.
BACKGROUND: Carbon dioxide (CO2) pneumoperitoneum (PP) increases mean arterial blood pressure (MAP) and systemic vascular resistance (SVR) but decreases stroke volume (SV) and cardiac output (CO). This study evaluated the hemodynamic effects of elevated intraabdominal pressure (IAP) occurring during laparoscopic donor nephrectomy (LDN). METHODS: Twenty-two patients undergoing LDN were investigated and hemodynamic parameters, P(v)CO2) (carbon dioxide partial pressure), and VCO2 (carbon dioxide production) were monitored during the procedure. Before and after PP, IAP was raised from 12 to 20 mmHg and the hemodynamic effects were measured every 30 s. RESULTS: During IAP of 12 mmHg and stable serum CO2, there was no change in SV compared to preinsufflation levels. When IAP was elevated from 12 to 20 mmHg, SV initially decreased (p < 05), followed by an increase in MAP and SVR (p < 0.05). CONCLUSION: This study shows that with the fluid and ventilation protocol used, PP has no significant effect on SV at an IAP of 12 mmHg, whereas increasing IAP to 20 mmHg does. In this study, the hemodynamic effects induced by CO2 PP of 12 mmHg are not due to changes in serum CO2. Compression of the venous system during a PP of 20 mmHg reduces preload, with an subsequent increase in SVR.
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During the first generalised epileptic attack, a patient suffered a humerus fracture which necessitated an operation. This patient also had a history of spontaneous lung emboli and an elevated anti-cardiolipin plasma level for which coumarin was prescribed but was stopped preoperatively. After induction of general anaesthesia for a total shoulder arthroplasty, the patient became hypotensive and the bispectral index recorded perioperatively dropped to 0. Postoperatively, the patient developed signs of a unilateral borderzone cerebral infarct in the area of the medial cerebral artery. The possible pathomechanisms involved are discussed. In cases of known cerebral pathology intraoperative hypotension should be avoided by at all costs. Patients with increased anti-cardiolipin antibody levels and who suffer from epileptic attacks have an increased risk of thromboembolic events.
BACKGROUND: Cardiac troponin T (cTnT) is a sensitive and specific marker for myocardial injury, but elevations of cTnT without clinical evidence of ischemia and persistent or new electrocardiographic (ECG) abnormalities are common in patients undergoing major vascular surgery. We explored the long-term prognostic value of cTnT levels in these patients. METHODS: A follow-up study was conducted between 1996-2000 in 393 patients who underwent successful aortic or infrainguinal vascular surgery and routine sampling of cTnT. Patients were followed until May 2003 (median of 4 years [25th-75th percentile, 2.8-5.3 years]). Total creatine kinase (CK), CK-MB, and cTnT were routinely screened in all patients, and included sampling after surgery and the mornings of postoperative days 2, 3 and 7. Electrocardiograms were also routinely evaluated for sign of ischemia. An elevated cTnT was defined as serum concentrations >/=0.1 ng/ml in any of these samples. All-cause mortality was evaluated during long-term follow-up. RESULTS: Eighty patients (20%) had late death. The incidence of all-cause mortality (41% vs. 17%; p<0.001) was significantly higher in patients with an elevated cTnT level compared to patients with normal cTnT. After adjustment for baseline clinical characteristics, the association between an elevated cTnT level and increased incidence of all-cause mortality (adjusted hazard ratio, 1.9; 95% CI, 1.1-3.1) persisted. Elevated cTnT had significant prognostic value in patients with and without renal dysfunction, abnormal levels of CK-MB, and in patients with transient ECG abnormalities. CONCLUSIONS: Elevated cTnT levels are associated with an increased incidence of all-cause mortality in patients undergoing major vascular surgery.
OBJECTIVE: To investigate the combined beneficial effect of statin and beta-blocker use on perioperative mortality and myocardial infarction (MI) in patients undergoing abdominal aortic aneurysm surgery (AAA). BACKGROUND: Patients undergoing elective AAA-surgery identified by clinical risk factors and dobutamine stress echocardiography (DSE) as being at high-risk often have considerable cardiac complication rate despite the use of beta-blockers. METHODS: We studied 570 patients (mean age 69+/-9 years, 486 males) who underwent AAA-surgery between 1991 and 2001 at the Erasmus MC. Patients were evaluated for clinical risk factors (age>70 years, histories of MI, angina, diabetes mellitus, stroke, renal failure, heart failure and pulmonary disease), DSE, statin and beta-blocker use. The main outcome was a composite of perioperative mortality and MI within 30 days of surgery. RESULTS: Perioperative mortality or MI occurred in 51 (8.9%) patients. The incidence of the composite endpoint was significantly lower in statin users compared to nonusers (3.7% vs. 11.0%; crude odds ratio (OR): 0.31, 95% confidence interval (CI): 0.13-0.74; p=0.01). After correcting for other covariates, the association between statin use and reduced incidence of the composite endpoint remained unchanged (OR: 0.24, 95% CI: 0.10-0.70; p=0.01). Beta-blocker use was also associated with a significant reduction in the composite endpoint (OR: 0.24, 95% CI: 0.11-0.54). Patients using a combination of statins and beta-blockers appeared to be at lower risk for the composite endpoint across multiple cardiac risk strata; particularly patients with 3 or more risk factors experienced significantly lower perioperative events. CONCLUSIONS: A combination of statin and beta-blocker use in patients with AAA-surgery is associated with a reduced incidence of perioperative mortality and nonfatal MI particularly in patients at the highest risk.
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Alzheimer's disease is characterized by amyloid peptide formation and deposition, neurofibrillary tangles, central cholinergic dysfunction, and dementia; however, the relationship between these parameters is not well understood. We studied the effect of amyloid peptide formation and deposition on central cholinergic function in knock-in mice carrying the human amyloid precursor protein (APP) gene with the Swedish/London double mutation (APP-SL mice) which were crossbred with transgenic mice overexpressing normal (PS1wt) or mutated (M146L; PS1mut) human presenilin-1. APP-SLxPS1mut mice had increased levels of Abeta peptides at 10 months of age and amyloid plaques at 14 months of age while APP-SLxPS1wt mice did not have increased peptide levels and did not develop amyloid plaques. We used microdialysis in 15-27 months old mice to compare hippocampal acetylcholine (ACh) levels in the two mouse lines and found that extracellular ACh levels were slightly but significantly reduced in the APP-SLxPS1mut mice (-26%; P=0.044). Exploratory activity in the open field increased hippocampal ACh release by two-fold in both mouse lines; total and relative increases were not significantly different for the two strains under study. Similarly, infusion of scopolamine (1 microM) increased hippocampal ACh release to a similar extent (3-5-fold) in both groups. High-affinity choline uptake, a measure of the ACh turnover rate, was identical in both mouse lines. Neurons expressing choline acetyltransferase were increased in the septum of APP-SLxPS1mut mice (+26%; P=0.046). We conclude that amyloid peptide production causes a small decrease of extracellular ACh levels. The deposition of amyloid plaques, however, does not impair stimulated ACh release and proceeds without major changes of central cholinergic function.
We have presented, in a previous study, a new approach to detect, characterize and estimate the size of gaseous emboli, based on the nonlinear behavior of gaseous bubbles. In this study, a specific transducer design has been developed to be used for such a purpose. It is composed of two separate transmitting and receiving capabilities. The transmit part, consisting of a lead zirconate-titanate (PZT) material, emits at a frequency of 500 kHz and could generate pressures up to 410 kPa. On the top of the transmit surface, a thin polyvinylidene difluoride (PVDF) layer is glued and used for receiving frequencies from 250 kHz (f0/2) up to 2.5 MHz (5 f0). To evaluate this new design, ultrasonic measurements were carried out with gas bubbles with diameters ranging from 10 microm up to 90 microm and solid particles between 350 microm and 550 microm. The experimental results confirmed our previous findings: gaseous emboli with a diameter close to the resonance size scatter significantly at higher harmonic components (from the second harmonic up to the fifth), and bubbles with a diameter around twice the resonance size produce a subharmonic and/or an ultraharmonic component. Meanwhile, solid particles and other bubble sizes behave only linearly and their scattered spectrum appeared without any harmonics. The study demonstrates the utility of this approach in using a single transducer to detect and characterize selective gaseous emboli from other particles using their nonlinear behavior.
We retrospectively analyzed the prognostic significance of mixed chimerism and associated clinical parameters in 80 patients following unmanipulated allogenic stem cell transplantation. Chimerism studies were performed on marrow aspirates using fluorescent in situ hybridization and variable number tandem repeats techniques at day +30, day +90 and +12 months. The median overall survival (OS) was 24 months (range, 1-56 months). Mixed chimerism was found in 23, 28 and 14% of patients at day +30 (1 month), +90 (3 months), and +12 months, respectively. Day +30 chimerism studies failed to provide any prognostic information. Day +90 mixed chimeras (MC) had significantly higher relapse rates compared to day +90 complete chimeras (CC) at 6 months (P=0.03) and 18 months when compared to MC (P=0.03) following transplant. The median OS in day +90 MC and day+90 CC were, respectively (95% CI, 2-35 months), compared to 47 months (95% CI, 20-74 months) (P=0.02). In conclusion, chimerism studies on day +30 could be reserved for patients who fail to demonstrate engraftment. Day +90 MC had higher relapse rates and lower OS, and therefore may be considered for novel therapies and future studies.
The genome of the cichlid (teleost) fish Oreochromis niloticus contains a set of genes which encode group V C-type lectin proteins homologous to the mammalian NKG2/CD94 family of natural killer (NK) cell receptors. To determine the genomic organization of these killer cell-like receptor (KLR) genes, an O. niloticus BAC library was screened with a cDNA probe derived previously from an expressed sequence tag of the related cichlid species Paralabidochromis chilotes. Four distinct KLR-bearing BAC clones were analysed, three of which could be assembled into a contig. One of the clones was sequenced in its entirety, whereas the others were partially sequenced to identify the KLR loci borne by them. Altogether, 28 distinct KLR loci were identified, of which at least 26 occupy a single chromosomal region, the KLR complex. One half of the loci appear to be occupied by pseudogenes. Compared to the human NK cell receptor complex, the Oreochromis KLR complex is more compact and, apart from transposons, appears to contain only KLR loci. The gene density of the complex is one KLR locus per 18 kb of sequence. All the KLR loci constituting the complex are derived from a single most recent common ancestor, which is estimated to have existed 7.7 million years ago. The 180 kb of the determined sequence is a mosaic of blocks of similar segments reflecting a complex history of duplications, deletions and rearrangements. The transposons found in the sequenced part belong to the TC1, Xena, CR1 and TX1 families.
We report the pre-operative preparation and anaesthetic management for resection of an intracerebral tumour during awake craniotomy in a 9-year-old boy. We believe this is the youngest patient reported to have undergone this procedure. The challenges of sedation and psychological care throughout the procedure are discussed. We conclude that the procedure can be performed safely and that it seems unacceptable to uphold an age restriction. We believe that it is the individual level of development of the child that determines suitability for this type of surgery.
Group C streptococci (GCS) and group G beta-haemolytic streptococci (GGS) have caused well-documented epidemics of acute pharyngitis in children, but the importance of these organisms in causing endemic or sporadic pharyngitis is uncertain. The heterogeneity of GCS and GGS may obscure the role of certain subtypes, such as the large-colony-forming strains of group C (Streptococcus dysgalactiae subsp. equisimilis) or group G, in endemic pharyngitis. For a 1-year period, children (aged 6 months to 18 years) (n = 2085) who presented with pharyngitis to the children's hospital emergency department and two outpatient offices were enrolled in a cross-sectional study to ascertain the role of large-colony-forming GCS and GGS in acute pharyngitis. Control patients (n = 194) were children who presented to the same locations during the same time period with non-respiratory tract symptoms or to the orthopaedic cast clinic. Throat cultures were obtained by a standard reference method, and swabs were plated on Strep-Selective Agar. Lancefield grouping and species identification was performed on all beta-haemolytic isolates. In total, 65 (3%) large-colony-forming GCS and GGS strains were obtained from pharyngitis patients, and three (1.5%) were obtained from the control group (odds ratio 2.0; 95% confidence interval 0.6-6.1). The low isolation rate of large-colony-forming strains of GCS and GGS indicates that even if these organisms are associated with acute, sporadic pharyngitis in paediatric patients, they represent an unusual pathogen.
OBJECTIVE: Levels of glucose and lactate were measured in the brain by means of microdialysis in order to evaluate the effects of ventilator-induced hypocapnia and hypercapnia on brain metabolism in healthy non-brain-traumatized animals. DESIGN AND SETTING: Prospective animal study in a university laboratory. SUBJECTS: Eight adult Landrace/Yorkshire pigs. INTERVENTIONS: The microdialysis probe was inserted in the brain along with a multiparameter sensor and intracranial pressure (ICP) probe. The animals were ventilated in a pressure-controlled mode according to the open lung concept with an inspired oxygen fraction of 0.4/1.0. Starting at normoventilation (PaCO(2) +/-40 mmHg) two steps of both hypercapnia (PCO(2) +/- 70 and 100 mmHg) and hypocapnia (PaCO(2) +/- 20 and 30 mmHg) were performed. Under these conditions, brain glucose and lactate levels as well as brain oxygen (PbrO(2)), brain carbon dioxide (PbrCO(2)), brain pH (brpH), brain temperature and ICP were measured. RESULTS: At hypercapnia (PaCO(2) = 102.7 mmHg) there were no significant changes in brain glucose and lactate but there was a significant increase in PbrCO(2), PbrO(2) and ICP. In contrast, at hypocapnia (PCO(2) = 19.8 mmHg) there was a significant increase in brain lactate and a significant decrease in both brain glucose and PbrCO(2). CONCLUSIONS: Hypocapnia decreases brain glucose and increases brain lactate concentration, indicating anaerobic metabolism, whereas hypercapnia has no influence on levels of brain glucose and brain lactate.
OBJECTIVE: To evaluate the effectiveness of a lay delivered intervention to reduce Latino children's exposure to environmental tobacco smoke (ETS). The a priori hypothesis was that children living in households that were in the intervention group would have lower exposure over time than measurement only controls. DESIGN: A two group, randomised control trial was conducted. SETTING: Areas of San Diego county with a large Latino population. PARTICIPANTS: 143 Latino parent-child pairs. INTERVENTION: Trained bicultural and bilingual Latina lay community health advisors, or promotoras, conducted problem solving aimed at lowering the target child's exposure to ETS in the household. Six home and telephone sessions were delivered by the promotoras over a four month period. MAIN OUTCOME MEASURES: Outcome measures were collected at baseline, immediately post-intervention, three months post-intervention, and 12 months post-intervention. Four outcomes were considered: (1) parent's paper-and-pencil reports of the child's past month exposure; (2) hair samples from the child analysed for past month nicotine; (3) hair samples from the child analysed for past month cotinine; and (4) per cent confirmed reducers. RESULTS: There were no significant condition-by-time interactions, the term indicative of a differential intervention effect. Significant or near significant time main effects were seen for children's hair cotinine, per cent confirmed reducers, and, in particular, parent reports of exposure. CONCLUSIONS: Applying a lay promotora model to deliver the behavioural problem solving intervention unfortunately was not effective. A likely explanation relates to the difficulty of delivering a relatively complex intervention by lay women untrained in behaviour change theory and research methods.
The effects of altering the number and type of additional carbohydrate moieties on the pharmacokinetic and pharmacodynamic properties of FSH were examined in this report. A series of single-chain follitropins, containing variable numbers of additional N- (or O-) linked carbohydrates, were designed and expressed in Chinese hamster ovary cells. Proper folding, efficient receptor binding, and signal transduction were confirmed by in vitro assays. Pharmacokinetic and pharmacodynamic parameters were evaluated in immature female Sprague Dawley rats. Increasing the number of glycosylation sites with either N- (or O-) linked moieties extended the elimination half-life as much as 2-fold compared with recombinant human FSH (rhFSH). However, there was a maximum elimination half-life such that further glycosylation provided no additional lengthening of the half-life. Conversely, biopotency, as assessed by inhibin A levels 74 h post injection, and follicle production were significantly higher for the N-linked analogs. Rats stimulated with the longest acting analogs (either N- or O-linked) showed significantly higher ovarian weights than rats receiving a single injection of rhFSH. The analog containing four additional N-linked sites (rhFSH-N4) had the greatest number of large, preovulatory follicles. Although the half-life of rhFSH-N4 displayed no further enhancement beyond the other longest acting analogs, this analog exhibited significantly increased biopotency in rats. This work provides the basis for the generation of a series of reagents potentially useful for therapeutic applications.