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Biomedical subjects

B Seifert

Publications and source records attributed to B Seifert.

At least 37 records · Page 2Linked to original sources

[Which lymphadenectomy in papillary thyroid gland carcinoma?].

BACKGROUND: The optimal treatment of papillary thyroid carcinoma (PTC) is still debated, also with respect to nodal treatment. METHOD: Retrospective analysis of a personal series of 159 patients with PTC, with respect to nodal disease, follow up 1-27 (mean 8) years. RESULTS: In 42 patients with clinical, macroscopic nodal disease (cN1) a therapeutic lymphadenectomy was performed, with pN1 status in 41 (98%) patients. 117 patients had no clinical or intraoperative suspicion of nodal involvement (cN0), with occult nodal disease in 5/29 (17%) patients undergoing prophylactic (elective) lymphadenectomy, and in 2/88 (2.3%) patients without primary lymphadenectomy (metachronous nodal disease) (p < 0.005). Nodal recurrences were observed (1-5 years after primary treatment for cure) in 5/42 (12%) pN1 and in 3/114 (2.6%) cN0, pN0 tumors (p = 0.009), with unfavourable outcome in 2 and 1 patients, respectively. The 20-year tumor specific survival was 100% in TNM I + II (low risk) patients (including pN1 and N0 tumors); the survival rate was deteriorated by stage pN1 vs. N0 in TNM high risk patients (50% vs. 86%; p = 0.03). DISCUSSION: The intraoperative macroscopic staging (cN) remains important:--clinical nodal disease warrants a systematic node dissection (microdissection), for preventing (curable or serious) nodal recurrences. Occult nodal disease does not evolve frequently in clinical nodal recurrence. A less radical (and only central) prophylactic lymphadenectomy, avoiding surgical morbidity, may be oncologically adequate. More sensitive detection of nodal positivity (frozen section of sampling tissue or sentinel nodes, immunohistochemistry) appears not rationale. In pN0, cN0 tumors use of prophylactic 131I may represent overtreatment, and follow up controls may be conducted less rigorously.

Adult↗

Detection of submucosal gastric fundal varices with multi-detector row CT angiography.

BACKGROUND AND AIM: The diagnosis of submucosal fundal varices is challenging. Currently, endoscopy and endoscopic ultrasound (EUS) are considered most useful for this purpose. The aim of this study was to evaluate if multi-detector row CT (MDCT) angiography contributes to the diagnosis of submucosal fundal varices. PATIENTS AND METHODS: Twenty two patients with endoscopically suspected fundal varices were prospectively included in the study. All patients underwent EUS and MDCT angiography. Levels of agreement between EUS and MDCT angiography for the detection of submucosal and perigastric fundal varices were evaluated by three blinded independent readers. In addition, variceal size and location, as well as afferent and efferent vessels of the submucosal varices, were determined. RESULTS: Good or excellent image quality of MDCT angiography was obtained in 21/22 patients (95%). Based on EUS, submucosal varices were detected in 16 of 22 patients (73%) and perigastric varices in 22/22 patients (100%). Using MDCT angiography, the presence of submucosal varices was confirmed in all of these 16 patients by all three readers. Perigastric varices were also confirmed in all 22 patients by all three readers. In addition, all three readers noted the presence of a submucosal varix in an additional patient which was not detected on initial EUS. MDCT angiography showed an excellent interobserver reliability with regard to variceal diameter (kappa=0.90) and variceal location (kappa=0.94). Based on MDCT angiography, afferent and efferent vessels of submucosal varices included the left gastric vein in 11 (65%), the posterior/short gastric veins in 15 (88%), gastrorenal shunts in 10 (59%), the left inferior phrenic vein in six (35%), and the left pericardiophrenic vein in six (35%) of 17 patients. CONCLUSIONS: MDCT angiography is equivalent to EUS in terms of detection and characterisation of fundal varices, in particular with regard to the distinction between submucosal and perigastric fundal varices.

Adult↗

[General medicine as an academic discipline].

The aim of the article is to show emerging changes in the health care, which will require some adaptation of curricula of medical faculties. It also considers the role of general practice in those changes and it emphasizes the potential of general practice for the undergraduate medical education and for the primary care research. Three questions are discussed: What can the subject of general practice offer to medical faculties? What can the medical faculties do for the general practice? At universities, the discipline "General practice" should become, similarly to the real health care, the first bridge between books and the live human. At higher classes, it should represent a clinical field with its position in the health care system, with its definition and characteristics. Similarly to other countries, general practice should offer all attributes of a medical branch for the full accomplishment of medicals, including their scientific work and teaching. It would require further developing of its academic basis. Society will be then awarded with higher quality of medical care offered by general practitioners.

Czech Republic↗

Outcome of the first 3-years of a DNA-based neonatal screening program for glutaric acidemia type 1 in Manitoba and northwestern Ontario, Canada.

Glutaric acidemia type 1 (GA1) is overrepresented in the aboriginal population of Island Lake, Manitoba, and northwestern Ontario who speak the Ojibway-Cree (Oji-Cree) dialect. The carrier frequency in these communities has been predicted to be as high as 1 in 10 individuals. Prior to beginning newborn screening for GA1 in May 1998, 18 of 20 affected patients diagnosed at this center have been from these high-risk communities. Most have followed an acute encephalopathic course with permanent neurologic sequelae and high mortality. They excrete small amounts of glutaric acid and 3-hydroxyglutaric acid and have significant residual enzyme activity. A single homozygous mutation in glutaryl-CoA-dehydrogenase (GCDH IVS-1 + 5g right arrow t) has been identified in this population. DNA-based newborn screening targeted to our high-risk communities was begun in order to provide presymptomatic detection and treatment of affected patients. Of the first 1176 newborns screened, 4 affected infants were identified and treated with a low-protein diet, carnitine, and riboflavin. All 4 infants have required numerous hospitalizations for treatment of intercurrent illnesses. Eventually, 3 infants presented with acute dystonic encephalopathy and seizures along with permanent neurological sequelae. One of these infants died unexpectedly at home at 18 months of age. The fourth, now 9 months old, has had a gastrostomy tube placed to facilitate fluid replacement in addition to a standard treatment protocol and is doing well. The reasons for our initial disappointing outcomes in the first 3 of 4 affected babies are likely multiple. Based on our early experience and that of other centers screening newborns for GA1, current therapeutic strategies may be insufficient in preventing the occurrence of neurologic sequelae in some children. An incomplete understanding of the neurotoxic mechanisms underlying this devastating disorder hampers effective management.

Canada↗

Predictors of complications in acute type B aortic dissection.

OBJECTIVES: Medical treatment is generally advocated for patients with acute type B aortic dissection without complications. The objective of this retrospective analysis was to determine whether there are any initial findings that can help predict the long-term course of the disease. METHODS: Case records of the 130 patients treated for type B aortic dissection between 1988 and 1997 were reviewed; 41 (31%) were operated on in the acute phase (<14 days), 31 (24%) were operated on in the chronic phase and 58 (45%) were treated medically. RESULTS: Overall acute mortality was 10.8%; 22% for patients operated on in the early phase and 5.6% for medically treated patients. Age (P=0.002), persistent pain (P=0.01) and malperfusion (P=0.001) were significant independent predictors of the need for surgery. Paraplegia/para paresis (P=0.0001), leg ischaemia (P=0.003), pleural effusion (P=0.003), rupture (P=0.0001), shock (P=0.0001), age (P=0.003), cardiac failure (P=0.002) and aortic diameter >4.5 cm (P=0.002) were significant predictors of poor survival. Age and shock also emerged as independent risk factors. Patients without malperfusion (P=0.0001), pleural effusion (P=0.003), rupture (P=0.0001) and shock (P=0.0001) had a significantly better event-free survival (freedom from repeat surgery and death). The actuarial survival rate for high-risk patients (malperfusion, rupture, shock) was 62% at 1 year and 40% at 5 years; the corresponding values for low-risk patients were 94 and 84%, respectively. CONCLUSIONS: Rupture, shock and malperfusion are significant predictors of poor survival in patients with acute type B aortic dissection.

Adult↗

Polyetherimide: a new membrane-forming polymer for biomedical applications.

Membranes for biohybrid organs such as the biohybrid liver support system have to face 2 different environments, namely blood and tissue cells. Accordingly, the respective membrane surfaces must have optimal properties in terms of biocompatibility for blood or tissue. Flat membranes prepared by a phase inversion process from polyetherimide were modified by binding of tris-(hydroxymethyl)-aminomethane to obtain a surface with hydroxyl groups by binding of polyethylene imine to attach a hydrophilic macromolecule with amine groups useful as a spacer for later bonding of further ligands and by attachment of heparin. The binding of the different ligands was successful as monitored by different physicochemical methods. The blood response of plain polyetherimide was comparable to that of polyacrylonitrile, and it could be further improved by the binding of heparin. The tissue compatibility of polyetherimide and its different modifications was compared with commercial cell culture substrate membranes (Millicell) and found to be comparable for polyetherimide and even better after the modification with tris-(hydroxymethyl)-aminomethane. In conclusion, polyetherimide seems to be an interesting material for the production of membranes for application in biohybrid organ systems.

Complement Activation↗

Quantification of fetomaternal hemorrhage by fluorescence microscopy is equivalent to flow cytometry.

BACKGROUND: The quantification of fetal cells in the maternal circulation remains an important goal to determine the amount of anti-D necessary to prevent active immunization of a D- mother giving birth to a D+ baby. Underestimation of fetomaternal hemorrhage (FMH) results in inefficient anti-D prophylaxis and maternal immunization; overestimation of FMH results in higher doses of passively transferred anti-D, higher costs, and the risk of disease transmission. Thus, a reliable method to quantitatively assess FMH is necessary. STUDY DESIGN AND METHODS: Serial dilutions of artificial FMH were quantitatively measured by three different methods: flow cytometry, fluorescence microscopy (each after anti-D staining), and by the Kleihauer-Betke test. The accuracy and precision of the three methods were compared by statistical analysis. RESULTS: Fluorescence microscopy and flow cytometry were comparably accurate and precise in quantifying FMH. In contrast, the accuracy of the Kleihauer-Betke test was poor, resulting in substantial overestimation of FMH in the samples with lower fetal cell concentrations. CONCLUSION: Anti-D flow cytometry and fluorescence microscopy for detection of fetal cells offer equally reliable and precise methods in contrast to the Kleihauer-Betke test. Fluorescence microscopy may be established as standard to quantify FMH in clinical practice because it is comparable to flow cytometry; in addition, it is time saving and is less expensive.

Adult↗

ICD implantation with and without combined myocardial revascularisation--incidence of ICD therapy and late survival.

BACKGROUND: Our aim was to evaluate the occurrence of implanted cardioverter-defibrillator (ICD) shock and antitachycardia pacing (ATP), the effect of ICD therapies on mortality and the impact of revascularisation strategies on arrhythmic events. PATIENTS AND METHODS: We investigated 130 CAD patients undergoing ICD implantation between 1984 and 1999. RESULTS: Freedom of shock was 66 +/- 7 %, 48 +/- 9 % and 48 +/- 9 % after 1, 3 and 5 years in patients with revascularisation and 62 +/- 8 %, 43 +/- 8 % and 23 +/- 11 % in patients without revascularisation, respectively; p = n. s. Freedom from ATP was similar in both groups - in patients with revascularisation, 64 +/- 6 %, 58 +/- 7 % and 58 +/- 7 % and without revascularisation 56 +/- 8 %, 51 +/- 9 % and 38 +/- 10 %, respectively; p = n. s. There were no significant differences in cumulative survival between patients with and without revascularisation; p = n. s. CONCLUSIONS: CAD patients with VT/VF and with implanted ICD have, despite successful revascularisation, the same rate of device therapy and mortality as patients without an indication of revascularisation. This implies that patients with chronic ischemic heart disease and ventricular tachyarrhythmias continue to be at risk of sudden death after CABG/PTCA; evaluation for ICD implantation is warranted.

Angioplasty, Balloon, Coronary↗

In patients with deep-vein thrombosis elevated levels of factor VIII correlate only with von Willebrand factor but not other endothelial cell-derived coagulation and fibrinolysis proteins.

Several studies have shown that patients with venous thrombosis have elevated levels of factor VIII (FVIII) at an increased frequency. Most such patients also have high von Willebrand factor (vWF) levels. Since vWF is synthesized by the vascular endothelium, we hypothesized that elevated FVIII levels would also be associated with an increase of other endothelial cell-derived coagulation proteins suggesting perturbation of the endothelium. In 100 healthy individuals and 129 patients with venous thromboembolism, we have determined antigenic FVIII levels along with several endothelial proteins including vWF, soluble thrombomodulin (sTM), tissue-type plasminogen activator (t-PA), and plasminogen activator inhibitor 1 (PAI-1). Levels of FVIII, vWF, PAI-1 and t-PA were significantly increased in patients compared with the controls (FVIII, vWF, and PAI-1,P < 0.001; t-PA, P < 0.05). Levels of sTM, however, were higher in the controls than in the patients (P < 0.001). Whereas the FVIII levels correlated well with the vWF levels in the patients (correlation, 0.61; P < 0.001) and the controls (correlation, 0.70; P < 0.001), there was neither a relevant correlation between FVIII and sTM, PAI-1, and t-PA, nor between vWF and sTM, PAI-1, and t-PA in the patients and the controls. In conclusion, although levels of PAI-1 and t-PA can be found, on average, at increased levels in patients with thrombosis, FVIII levels correlate only with vWF but not other endothelial cell-derived coagulation and fibrinolysis proteins including sTM, PAI-1, and t-PA.

Adult↗

Mutations of the serine protease inhibitor, Kazal type 1 gene, in patients with idiopathic chronic pancreatitis.

OBJECTIVE: The pathogenesis of chronic pancreatitis (CP) is poorly understood. Genetic studies revealed mutations in the cationic trypsinogen gene and an increased frequency of cystic fibrosis gene mutations in patients with CP. Recently, a point mutation (N34S) in the gene encoding the serine protease inhibitor, Kazal type 1 (SPINK1), was found in approximately 20% of patients with CP. The aim of our study was to determine the frequency of the N34S SPINKI gene mutation in a well-defined patient cohort with idiopathic CP (ICP) and to compare the incidence with healthy controls. In addition, we investigated the impact of this mutation on the long-term course of CP. METHODS: Fourteen patients with early-onset and four patients with late-onset CP of our well-defined pancreatitis cohort were enrolled in the present study, and 397 healthy individuals served as a control population. Coding exonic and the flanking intronic sequences of SPINK1 were investigated by direct DNA sequencing. The mutations found were confirmed by melting curve analysis. In addition, the N34S mutation was detected by analyzing the DNA fragments generated by digestion with restriction enzyme TspR I. Clinical data of patients with the N34S mutation were compared with those without mutations. RESULTS: The N34S mutation was detected in six of 14 (43%) patients with early-onset ICP. One patient was homozygous, and five patients were heterozygous for this mutation. The N34S mutation in a heterozygous state was found in four of 397 healthy controls (1.0%). The different allele frequency observed (seven of 28 vs four of 794) was significant (odds ratio = 66, 95% CI = 18-242, p < 0.0001). The clinical course was similar in patients with a mutation compared with those without a mutation. No other SPINKI mutations were detected. The N34S mutation was not found in patients with late-onset ICP. CONCLUSIONS: Our results indicate that the N34S mutation in the SPINKI gene is strongly associated with ICP, especially with the early-onset type. The natural course is similar in patients with mutations compared with SPINK1 mutation-negative patients. The N34S mutation may easily be screened for by restriction digestion with TspR I.

Adult↗

Oral premedication for operations on the face under local anesthesia: a placebo-controlled double-blind trial.

Modern strategies for preventing or controlling pain and anxiety demand a premedication for operations using local anesthesia and for those using sedation or general anesthesia. For optimal patient care, the premedication should be given orally and, with respect to the outpatient basis of the operations, should have a short recovery period. Midazolam, one of the most favored premedications for general anesthesia, has been recommended as a premedication for operations using local anesthesia as well. However, midazolam has only sedative-anxiolytic effects and does not reduce pain sensation, which should be mandatory for operations using local anesthesia. A further requirement is the maintenance of stable hemodynamics for the prevention of postoperative hematomas, especially in the face. For these reasons, another premedication meeting all requirements (anxiolysis, analgesia, and stable hemodynamics) was researched. A randomized, double-blind prospective study was performed from March of 1997 to June of 1998. Five groups totalling 150 patients were included in the study; each group contained 30 patients who had operations performed solely on the face. In the first four groups, the effect of midazolam (0.15 mg/kg(-1)), morphine (0.3 mg/kg(-1)), and clonidine (1.5 microg/kg(-1)) administered orally was compared with a placebo. The fifth group was the control group and received no premedication. To evaluate the effects of the premedications, a corresponding questionnaire was completed independently by the patient and surgeon. With regard to the anxiolytic or analgesic properties of the premedication, 61 percent of the patients preferred pain reduction to anxiety control, and 24 percent of patients preferred reduction of anxiety. The remainder insisted on a reduction of both properties (8 percent) or had no preference (7 percent). Reduction of anxiety was largest in the midazolam and the clonidine groups, but the difference was not significant. The least pain during the application of local anesthesia was experienced by the morphine group (37 percent) and the clonidine group (33 percent), in contrast to the midazolam group (60 percent) (p = 0.04). Morphine and clonidine met the requirements of pain reduction equally well. Nevertheless, considering the rate and intensity of adverse effects with respect to hemodynamic compromises, nausea, and emesis, clonidine is even better suited as an oral premedication for operations on the face using local anesthesia.

Administration, Oral↗

Differentiated thyroid carcinoma. Follow-up of 264 patients from one institution for up to 25 years.

UNLABELLED: The optimum treatment for differentiated thyroid carcinoma (DTC) is still debated. Results obtained using a selective treatment strategy for papillary (PTC) and follicular (FTC) thyroid carcinoma over 25 years in one institution are reported. 149 patients (mean age 46 yrs) had PTC in TNM stages I-IV in 58%, 26%, 15% and 1% respectively. Total thyroidectomy and remnant 131I ablation (43%) were carried out in TNM high-risk patients (stages III and IV) and in low-risk patients (I and II) at risk for a (curable) recurrence (stages pN1 and/or pT4). Hemi- or total thyroidectomy, without radioiodine, was used in 76% of pT1-3 N0 tumours (68%). Central and/or lateral lymphadenectomy was performed in 42% of patients (electively in the last 4 years). The mean follow-up was 7 years. RESULTS: 6 patients died of PTC and 8/143 patients treated for cure had a recurrence (6 nodal, 1 contralateral, 1 local). In low-risk patients--including 68% of patients aged > or = 45 yrs--the cause specific 25-year survival rate was 100%, vs. 62% (at 15 years) (p < 0.0001) in high-risk patients. In stage I and stage II the recurrence-free survival rates at 25 years were 95% and 100% respectively. Risk factors for recurrence were macroscopic (p < 0.0001) but not microscopic local invasion (pT4); stage pN1 (p = 0.0004). Only 1/107 patients initially judged node-negative had a nodal recurrence. FTC (n = 115; mean age 56 yrs; mean follow-up 8 yrs): Cause-related death (n = 8) or serious recurrence (n = 3) occurred in 10/53 grossly invasive FTC, in 1/45 minimally invasive FTC with vascular invasion, and in none of 17 FTC with capsular invasion (CI) alone, under radical treatment (131I) in 75%, 33%, and 12% respectively. 20-year disease-free survival in grossly and in minimally invasive FTC was 78% and 95.5% respectively (p = 0.0007). Patients aged < 45 yrs and patients with minimally invasive FTC with CI alone (all ages) had 100% 20-year disease-free survival vs. 80% (p = 0.013) in the remainder. There was no curable recurrence in FTC. The ratio of grossly invasive FTC decreased (p < 0.0001) during the study period. CONCLUSIONS: Risk-0 groups may be defined and selected for a reduced extent of treatment (PTC pT1-3 N0; FTC < 45 yrs, or CI alone). Older (> or = 45 yrs) patients with PTC in stages I and II have an excellent prognosis (risk 0). With selective (therapeutic) lymphadenectomy the risk of nodal recurrence may be very low in node negative tumours, without use of radioiodine. Meticulous lymphadenectomy is indicated in pN1 tumours with nodal recurrences despite 131I (5/36 patients). The technique of capsular dissection for extracapsular total uni- or bilateral thyroidectomy provides excellent oncological and surgical results. A decrease in the incidence of FTC parallels a decrease in endemic goitre in Switzerland.

Adenoma↗

Comparison of effects of amphotericin B deoxycholate infused over 4 or 24 hours: randomised controlled trial.

OBJECTIVE: To test the hypothesis that amphotericin B deoxycholate is less toxic when given by continuous infusion than by conventional rapid infusion. DESIGN: Randomised, controlled, non-blinded, single centre study. SETTING: University hospital providing tertiary clinical care. PATIENTS: 80 mostly neutropenic patients with refractory fever and suspected or proved invasive fungal infections. INTERVENTION: Patients were randomised to receive 0.97 mg/kg amphotericin B by continuous infusion over 24 hours or 0.95 mg/kg by rapid infusion over four hours. MAIN OUTCOME MEASURES: Patients were evaluated for side effects related to infusion, nephrotoxicity, and mortality up to three months after treatment. Analysis was on an intention to treat basis. RESULTS: Patients in the continuous infusion group had fewer side effects and significantly reduced nephrotoxicity than those in the rapid infusion group. Overall mortality was higher during treatment and after three months' follow up in the rapid infusion than in the continuous infusion group. CONCLUSION: Continuous infusions of amphotericin B reduce nephrotoxicity and side effects related to infusion without increasing mortality.

Adolescent↗

TAP1 down-regulation in primary melanoma lesions: an independent marker of poor prognosis.

Melanoma tumor thickness is a major prognostic factor. Thin lesions, however, may metastasize, and sometimes thick tumors may not. To investigate the role of HLA class I-mediated antigen presentation, we correlated the expression of components of the antigen-processing machinery in primary melanoma lesions with their thickness and with the development of metastases. Seventeen formalin-fixed, paraffin-embedded primary melanomas thinner than 0.76 mm and 21 thicker than 1.50 mm were stained with anti-LMP2, -LMP7, -TAP1, -TAP2, -HLA class I and -beta2-microglobulin monoclonal antibodies. Twenty patients remained tumor-free in the follow-up period (10.5 +/- 1.8 years). Eighteen patients relapsed within a median period of 15.0 months following tumor excision. Expression of all markers in the tested lesions was down-regulated, the frequency ranging from about 40% for LMP and TAP subunits to about 70% for HLA class I antigens. Expression of all markers was not correlated with tumor thickness. Only TAP1 and TAP2 down-regulation was significantly (p = 0.026 and 0.042, respectively) correlated with the development of metastases. This correlation was independent of tumor thickness for TAP1. We suggest that TAP1 and probably TAP2 expression in primary lesions represents an independent prognostic marker in melanoma. Abnormalities in antigen presentation may account for the lack of absolute correlation between tumor thickness and prognosis.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

[Cardiovascular stress protection following anesthesia induction. Comparison of clonidine and esmolol].

Alpha-2-adrenoceptor-agonists as well as cardioselective betareceptor-antagonists have been shown to blunt stress response due to tracheal intubation. The purpose of our study was to investigate,whether clonidine or esmolol is more efficient to attenuate stress response due to intubation.44 patients were randomly assigned to receive either clonidine (n=22; 3 microg/kg) or esmolol (n=22; 2 mg/kg) immediately prior to a standardized induction of anaesthesia. Heart rate, arterial blood pressure, cardiac output, epinephrine and norepinephrine plasma concentrations were measured before,during and 10 min after intubation. Blood pressure was measured invasively and cardiac output was determined by transthoracic echocardiography. Absolute values and increase of mean arterial pressure and norepinephrine plasma concentrations were significantly less in the clonidine group (p<0,05). Clonidine (3 microg/kg) is more efficient than esmolol (2 mg/kg) in blunting stress response due to endotracheal intubation.

Adrenergic alpha-Agonists↗