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Biomedical subjects

N Vogt

Publications and source records attributed to N Vogt.

At least 19 recordsLinked to original sources
PubMed2002

Antibiotic duration for treating uncomplicated, symptomatic lower urinary tract infections in elderly women.

BACKGROUND: Urinary tract infections are common in elderly patients. Authors of non systematic literature reviews often recommend longer treatment durations (7-14 days) for older patients than for younger women, but the scientific evidence for such recommendations is not clear. OBJECTIVES: To determine the optimal duration of antibiotic treatment for uncomplicated symptomatic lower urinary tract infections in elderly women. SEARCH STRATEGY: We contacted known investigators and pharmaceutical companies marketing antibiotics used to treat urinary tract infections, screened the reference list of identified articles, reviews and books, and searched the following data bases: MEDLINE, EMBASE, CINAHL, Healthstar, Popline, Gerolit, Bioethics Line, The Cochrane Library, Dissertation Abstracts International, Index to Scientific & Technical Proceedings. SELECTION CRITERIA: All randomized controlled trials in which different treatment durations of oral antibiotics for uncomplicated symptomatic lower urinary tract infections in elderly women were compared. We excluded patients with fever or flank pain and those with complicating factors. Trials with treatment durations longer than 14 days or designed for prevention of urinary tract infection were also excluded. No language restriction was applied. DATA COLLECTION AND ANALYSIS: The quality of all selected trials was assessed and data extracted by the reviewers. Main outcome measures were persistence of urinary symptoms (short-term and long-term efficacy), effect on mental and functional status and adverse drug reactions. To compare the different treatment durations, we defined the following categories of duration: single dose, short course (3-6 days) and long course (7-14 days). Relative risk (RR) and 95% confidence intervals (CI) were calculated for each trial and outcome and were then combined using a random effects model. MAIN RESULTS: Thirteen trials were included in this review. Six trials compared single dose with short-term treatment (3-6 days), three studies single dose with long-term treatment (7-14 days) and four trials short-term with long term treatment. Eight trials also included younger patients, but provided a subgroup analysis for elderly women. The methodological quality of all trials was low. All trials reported results of bacteriological cure rate; less often clinical outcomes (e.g. improvement or cure of symptoms) were analyzed. Only five trials compared the same antibiotic given for a different length of time. We performed a separate analysis for these trials. The rate of persistent bacteriuria rate at short-term (two weeks post-treatment) was better in the longer treatment group (3-14 days) than in the single dose group (RR 1.84, 95% CI 1.18 to 2.86). However, the rate of persistent bacteria at long term and the clinical cure rate showed no statistically significant difference between the two groups. Patients showed a preference for single dose treatment (RR 0.73, 95% CI 0.66 to 0.88), however this was based on only one trial comparing the same antibiotic. The comparison of short (3-6 days) and longer treatments (7-14 days) did not show any significant difference, but the number of included studies and sample size were low. REVIEWER'S CONCLUSIONS: This review suggests that single dose antibiotic treatment is less effective but may be better accepted by the patients than longer treatment durations (3-14 days). In addition there was no significant difference between short course (3-6 days) versus longer course (7-14 days) antibiotics. The methodological quality of the identified trials was poor and the optimal treatment duration could not be determined. We therefore need more appropriately designed randomized controlled trials testing the effect, - on clinical relevant outcomes -, of different treatment durations of a given antibiotic in a strictly defined population of elderly women.

Aged↗
PubMed2002

Microdissection techniques for cancer analysis.

One difficulty in studying molecular changes of tumours has been the inability to isolate DNA and RNA from a homogeneous cell population. The combination of several new technologies should help overcome these hurdles. Microdissection is a technique for rapid and easy procurement of a pure cellular subpopulation away from its complex tissue milieu. Laser-assisted microdissection has recently been identified as a quick, simple and effective method by which microdissection of complex tissue specimens can be routinely performed for molecular analysis. With the advent of laser microdissection, cDNA libraries can be developed from pure cells obtained directly from stained neoplastic tissue, and microarrays of thousands of genes can now be used to examine gene expression in microdissected tumour tissue samples. This review will concentrate on the application of different microdissection techniques in the area of cancer research.

Cell Separation↗
PubMed2001

Genome instability in secondary solid tumors developing after radiotherapy of bilateral retinoblastoma.

Genome alterations of seven secondary tumors (five osteosarcomas, one malignant peripheral sheath nerve tumor, one leiomyosarcoma) occurring in the field of irradiation of patients treated for bilateral retinoblastoma have been studied. These patients were predisposed to develop radiation-induced tumors because of the presence of a germ line mutation in the retinoblastoma gene (RB1). Tumor cells were characterized by a high chromosome instability whereas microsatellites and minisatellites were found to be stable. In all tumors, the normal RB1 allele was lost with the corresponding chromosome 13, whereas the germ line mutated allele was retained. The two alleles of TP53 were inactivated, one by deletion of the short arm of chromosome 17, the other by mutation. As compared with non-radiation-induced tumors, the observed panel of TP53 mutations was uncommon with sites not recurrently found otherwise and a high rate of deletions (3/7). In these predisposed patients, the loss of the single normal allele of RB1 is rather due to the radiation-induced chromosome instability than a direct effect of ionizing radiation.

Cytogenetic Analysis↗
PubMed2001

[Droperidol and dimenhydrinate alone or in combination for prevention of postoperative nausea and vomiting].

BACKGROUND: Droperidol and dimenhydrinate are inexpensive antiemetic drugs. Droperidol, especially, has been studied extensively in the past, but there are no studies that used the combination of both drugs for prevention of postoperative nausea and vomiting (PONV). Thus, the aim of this randomised controlled and double-blinded study was to evaluate the antiemetic efficacy and the side effects of such a combination therapy. METHODS: 240 inpatients undergoing ENT surgery under general anaesthesia were randomised to receive one of four antiemetic regimes: placebo, dimenhydrinate (1 mg x kg-1), droperidol (15 micrograms x kg-1), or the combination of both drugs (droperidol 15 micrograms x kg-1 + dimenhydrinate 1 mg x kg-1) was administered after induction of anaesthesia and repeated 6 hours after the first administration. For general anaesthesia a standardised technique including benzodiazepine premedication, propofol, desflurane in N2O/O2, vecuronium, and a continuous infusion of remifentanil was used. Postoperative analgesia and antiemetic rescue medication were standardised. Episodes of vomiting, retching, nausea, and the need for additional antiemetics were recorded for 24 hours. The main goal of the study was to increase the number of patients who were completely free from PONV (chi 2-test with Fisher-Yates' correction). Furthermore, the severity of PONV was analysed using a standardised scoring algorithm. RESULTS: Data of 227 patients could be analysed. The incidence of patients who suffered from PONV was 41.3% (95%-confidence interval: 29-55%) in the placebo-group. Dimenhydrinate alone reduced PONV to 34.5% (95%-CI: 22-48%). This marginal effect and the effect of droperidol (PONV: 26.4% (95%-CI: 15-40%)) could not be proven statistically, since the power of the study was too small. The combination of both drugs decreased PONV to 19.6% (95%-CI: 10-32%) and also reduced the severity of the symptoms to a clinically acceptable level. CONCLUSION: Dimenhydrinate failed to reduce the incidence and severity of PONV. The efficiency of droperidol given alone was within the ranges previously known from metaanalytic data. The combination of both drugs showed a moderate synergistic effect.

Adult↗
PubMed2000

Midazolam sedation for upper gastrointestinal endoscopy in older persons: a randomized, double-blind, placebo-controlled study.

OBJECTIVES: To investigate the benefits and risks of using midazolam for sedation during upper gastrointestinal endoscopic procedures in older persons. DESIGN: Randomized, double-blind, placebo-controlled study. SETTING: A 304-bed geriatric university hospital. PATIENTS: Sixty-five geriatric inpatients (mean age 84 +/- 7) undergoing gastroscopy. INTERVENTION: Sedation with either midazolam (30 microg/kg IV) or saline (placebo). All patients received supplemental oxygen during the procedure (2 L/minute). MEASUREMENTS AND RESULTS: Patients' recall of their tolerance to the exam (categorical scale) and pain score were significantly in favor of midazolam at 2 and 24 hours. Multivariate analysis at 2 hours showed that midazolam increased the probability of good tolerance (odds ratio (OR) = 19.3; 95% confidence interval (CI) 2.2-170.4, P = .008). Circumstantial amnesia occurred at 24 hours in 84% (midazolam) versus 27% (placebo) (P < .001). With midazolam, mean sedation time was 83 +/- 13 minutes and mean arterial pressure (MAP) was about 10 mm Hg lower without clinically significant hypotension. Hypoxemia (SaO2 < 92%) was more frequent in the midazolam group after endoscopy (44% vs. 18%, P = .033), but no major desaturation was observed. Cognitive function (Mini-Mental State Exam, MMSE) was similar before and 2 and 24 hours after the exam in both groups. Acute confusion was observed in two patients (1 midazolam, 1 placebo). In multivariate analysis, midazolam was associated with a higher risk of hypoxemia after endoscopy (OR = 3.5; 95% CI 1.1-10.8, P = .029) but not of confusion. CONCLUSIONS: Under adequate surveillance, the benefits in terms of tolerance to the procedure of low-dose midazolam for upper gastrointestinal endoscopic sedation outweigh the risks in older people.

Aged↗
PubMed2000

What's the basis for treating infections your way? Quality assessment of review articles on the treatment of urinary and respiratory tract infections in older people.

OBJECTIVE: To assess the quality of readily available review articles on urinary and respiratory tract infections in older people. METHODS: Data sources were articles identified by MEDLINE search (1988-1998), review of the bibliographies of identified publications, textbooks from the library of a geriatric university hospital, and booklets with general guidelines on antibiotic therapy. Selection was made of review articles or book chapters about urinary and/or respiratory tract infections in older people that were readily available, ie, in Swiss medical libraries. Quality was assessed according to clinical applicability of the recommendations, methodology of the review, type of literature cited in the bibliography, and age of the population included in these reference articles. RESULTS: Only 13 of 29 (45%) review articles about urinary tract infections and seven of 29 (24%) articles about respiratory tract infections satisfied our criteria of applicability. Specifically, dosage, route of administration, and treatment duration were often not described. The overall methodological quality was low (mean score 1.9 +/- 1.0 on a scale of 9). No review specified the methods used to identify, select, and validate included information. Authors of the review articles quoted an important number of other review articles and only a small number of clinical trials. Less than one-quarter of these clinical trials actually comprised primarily an older population. CONCLUSIONS: Review articles on treatment of common infectious diseases in older people are often neither clinically applicable nor of good methodological quality. Therefore, more systematic review articles regarding treatment of older patients, as well as evidence-based practice guidelines, are needed.

Geriatrics↗
PubMed2000

DNA methylation and chromosome instability in lymphoblastoid cell lines.

In order to gain more insight into the relationships between DNA methylation and genome stability, chromosomal and molecular evolutions of four Epstein-Barr virus-transformed human lymphoblastoid cell lines were followed in culture for more than 2 yr. The four cell lines underwent early, strong overall demethylation of the genome. The classical satellite-rich, heterochromatic,juxtacentromeric regions of chromosomes 1, 9, and 16 and the distal part of the long arm of the Y chromosome displayed specific behavior with time in culture. In two cell lines, they underwent a strong demethylation, involving successively chromosomes Y, 9, 16, and 1, whereas in the two other cell lines, they remained heavily methylated. For classical satellite 2-rich heterochromatic regions of chromosomes 1 and 16, a direct relationship could be established between their demethylation, their undercondensation at metaphase, and their involvement in non-clonal rearrangements. Unstable sites distributed along the whole chromosomes were found only when the heterochromatic regions of chromosomes 1 and 16 were unstable. The classical satellite 3-rich heterochromatic region of chromosomes 9 and Y, despite their strong demethylation, remained condensed and stable. Genome demethylation and chromosome instability could not be related to variations in mRNA amounts of the DNA methyltransferases DNMT1, DNMT3A, and DNMT3B and DNA demethylase. These data suggest that the influence of DNA demethylation on chromosome stability is modulated by a sequence-specific chromatin structure.

Ataxia Telangiectasia↗
PubMed1999

DNA methylation and chromosome instability in breast cancer cell lines.

We show that in a series of eight breast cancer cell lines, a direct relationship exists between the overall DNA demethylation and the percentage of rearranged chromosomes, except for cell lines with a highly rearranged genome which can be weakly demethylated. A real time fluorescent detection method was used to quantify by reverse transcription-PCR the expression of the DNA methyltransferase 1 and of the newly discovered DNA demethylase. The overall DNA methylation status seems to result from a complex interplay between the expression of these two genes. Our results suggest that in these tumor cells, the overall DNA demethylation is implicated in one of the mechanisms at the origin of the genome instability and that besides the role of the DNA methyltransferase 1, that of the DNA demethylase may be essential in the control of DNA methylation.

Breast Neoplasms↗
PubMed1999

Peri-operative tolerance to large-dose 6% HES 200/0.5 in major urological procedures compared with 5% human albumin.

We studied the long-term efficacy and safety of medium-molecular-weight hydroxyethyl starch (HES) administered in doses above 20 ml.kg-1 during major blood replacement therapy. Blood replacement for 50 patients used 6% HES 200/0.5 (HES group) or 5% albumin (ALB group) and additional blood components according to a defined protocol. We compared safety, efficacy and costs in 4 peri-operative days. Colloid administration on the day of surgery was 38.4 ml.kg-1 (HES group) and 35.1 ml.kg-1 (ALB group). Haemodynamic, coagulation and renal function parameters were similar. Although total serum protein was still different on the third postoperative day (53.45 gl-1 (HES group) and 60.6 gl-1 (ALB group) (p < 0.01)) the colloid osmotic pressure always remained above 19.5 (2.5) mmHg (HES group). Blood loss (3810 (1632) ml (HES group) and 3455 (1733) ml (ALB group)) and the requirement for blood components was comparable. Costs were reduced by 35% (p < 0.05) in the HES group. We conclude that using 6% HES 200/0.5 as the only colloid for treatment even of large blood loss is a safe and economic alternative to albumin.

Adult↗
PubMed1998

GAC1, a new member of the leucine-rich repeat superfamily on chromosome band 1q32.1, is amplified and overexpressed in malignant gliomas.

We have used two-dimensional electrophoresis of enzyme-digested genomic DNA to identify a novel gene GAC1, which maps at 1q32.1 and which is overexpressed in malignant gliomas in which it is amplified. GAC1 encodes a protein which belongs to the leucine-rich repeat superfamily. Amplification and overexpression of GAC1 was demonstrated in two of eight tumors where amplifications were previously evidenced by comparative genomic hybridization (one glioblastoma multiforme and one anaplastic astrocytoma), and in one of eight unselected glioblastomas multiforme. GAC1 exhibits sequence homology with other proteins which function as cell-adhesion molecules or as signal transduction receptor and is a likely candidate for the target gene in the 1q32.1 amplicon in malignant gliomas.

Amino Acid Sequence↗
PubMed1998

[Antibiotic utilization in a university geriatric hospital and drug formularies].

UNLABELLED: Inappropriate use of antibiotics needlessly increases drug expenditures, enhances the emergence of antimicrobial resistance in hospitals and heightens the risk of toxicity, especially in elderly patients. This population is very sensitive to inappropriate drug treatment because of pharmacological and pharmacokinetic changes, reduced homeostatic functional reserve, multiple underlying diseases (e.g. renal failure) and polypharmacy (leading to drug interactions and side effects). To assess antibiotic prescription in a geriatric university hospital with a restrictive drug formulary, we analyzed data extracted from the Drug Kardex (a standardized synthesis of all prescribed medicines) during 4 cross-sectional drug utilization studies, carried out in 1996 on all hospitalized patients. RESULTS: 1138 patients' Kardex have been analyzed. 20% of these patients received one or more antibiotic treatments. In total 268 antibiotic treatments (AB) were prescribed, 84 in March, 44 in June, 71 in September and 66 in December. 21 different AB were used, the five most frequently prescribed AB being amoxycillin-clavulanic acid, ceftriaxone, ciprofloxacin, metronidazole, co-trimoxazole and representing 69% of all AB. Most of the AB were given in an oral form (63%) and in one standard dose. Dose adjustments in these very old patients with a high percentage of renal failure were apparently rarely done. The choice of rather broad spectrum AB may be due to the fact that obtaining an appropriate bacteriological culture from elderly patients with respiratory tract infections is difficult, but was also due to a lack of diagnostic subcategorization of the infection. Undesirable effects of the restrictive drug formulary were also noted: large utilization of ciprofloxacine (only fluoroquinolone on the hospital's drug list) for urinary tract infections instead of other more appropriate antibiotics. CONCLUSION: It is important to individualize antibiotic drug therapy with respect to underlying diseases, site of infection and antibiotic sensitivity patterns, especially in elderly patients. Restrictive hospital drug formularies are not sufficient to assure rational drug use, but should be associated with broader educative measures.

Aged↗
PubMed1998

[Individualized drug therapy in geriatrics].

The process of modifying standard therapy to fit the needs of elderly patients calls upon physicians' interpersonal skills as well as their knowledge of normal and pathological aging and of clinical geronto-pharmacology. An individualized treatment plan is a synthesis of very subjective elements (such as the choice between painful curative treatment and less taxing but merely palliative treatment, or the establishment of treatment priorities) and more objective data such as renal function or drug characteristics. The reasons for individualizing therapy in the elderly patient, and how to achieve this, are reviewed.

Aged↗
PubMed1998

Omeprazole-induced hepatotoxicity? A case report.

CASE REPORT: We observed a serious symptomatic hepatocellular liver injury in an 85-year-old man treated with omeprazole for many years. Peak values for AST, ALT and AP were 1542 U/l (normal range 14-50), 1236 U/l (11-60) and 154 U/l (30-125) respectively. Abdominal CT scan was normal and viral serologic testing was negative. Omeprazole was discontinued and liver enzymes normalized in 12 days. The patient was known to suffer from ischemic heart disease and had had a myocardial infarction 6 months previously. He was reexposed to omeprazole and the level of liver enzymes rose again and normalized after stopping omeprazole. Despite the improvement of his liver function, the patient died 5 days later due to chronic congestive heart failure. DISCUSSION: Five cases of omeprazole-induced liver injury have been reported to the Swiss Drug Regulatory Agency since 1990, among them two of cholestatic hepatitis and one of hepatic failure. The WHO Data Base has collected 13,630 ADRs related to omeprazole, with more than 80 cases of hepatitis, 60 of jaundice and about 40 of cholestatic hepatitis. In contrast, only one case of severe symptomatic hepatotoxicity is described in the literature. Clinical studies reported minimal increase of liver enzymes only, in 1-5% of cases. CONCLUSION: This case with reexposure, together with those reported internationally, suggests that hepatitis is a possible but obviously rare complication of omeprazole treatment.

Journal Article↗
PubMed1998

Ibuprofen does not impair renal function in patients undergoing infrarenal aortic surgery with epidural anaesthesia.

OBJECTIVE: To investigate the effect of preoperative ibuprofen administration on renal function during and after infrarenal aortic surgery under thoracolumbar epidural anaesthesia (EPA). DESIGN: A prospective randomised, double-blinded clinical study. SETTING: Operation room and intensive care unit in a university hospital. PATIENTS: Twenty-six consecutive patients scheduled for elective infrarenal aortic surgery. INTERVENTIONS: The patients were prospectively randomised to receive 400 mg ibuprofen intravenously (i.v.) or a placebo aliquot before surgery. MEASUREMENTS AND RESULTS: We assessed renal function by calculating creatinine clearance, and fractional sodium excretion before surgery (baseline), 1 h after cross-clamping (intraoperative), 6 h after cross-clamping (postoperative) and 24 h after cross-clamping (on the 1 st postoperative day). At each point in time, we additionally registered haemodynamics and determined the plasma concentration of 6-keto-PGF1alpha (stable metabolite of prostacyclin, PGI2), bicyclic PGE2 (stable metabolite of PGE1 E2), active renin, aldosterone and vasopressin by radioimmunoassays. Throughout the observation period the renal function parameters mostly remained within the normal range without a significant difference between ibuprofen- and placebo-treated patients (creatinine clearance: baseline 41 +/- 3 vs 38 +/- 6, intraoperative 57 +/- 8 vs 64 +/- 11, postoperative 64 +/- 9 vs 56 +/- 9, first postoperative day 43 +/- 5 vs 47 +/- 6 ml x min x m(-2), means +/- SEM). The plasma levels of 6-keto-PGF1alpha (68 +/- 8 vs 380 +/- 71* ng x l(-1)), bicyclic PGE2 (57 +/- 5 vs 88 +/- 9* ng x l(-1)) and vasopressin (14 +/- 7 vs 45 +/- 10* ng x l(-1), p < 0.0125), however, were significantly higher during the intraoperative period in the placebo-treated patients. CONCLUSION: The inhibition of endogenous prostaglandin release by ibuprofen does not substantially impair renal function during infrarenal aortic surgery under EPA.

Aged↗
PubMed1998

Vasopressor hormone response following mesenteric traction during major abdominal surgery.

BACKGROUND: We investigated the vasopressor hormone response following mesenteric traction (MT) with hypotension due to prostacyclin (PGI2) release in patients undergoing abdominal surgery with a combined general and epidural anesthesia. METHODS: In a prospective, randomized, placebo-controlled study we administered 400 mg ibuprofen (i.v.) in 42 patients scheduled for abdominal surgery. General anesthesia was combined with epidural anesthesia (T4-L1). Before as well as 5, 15, 30, 45, and 90 min after MT we recorded plasma osmolality, hemodynamics and measured 6-keto-PGF1 alpha (stabile metabolite of PGI2), TXB2 (stabile metabolite of thromboxane A2) active renin, and arginine vasopressin (AVP) plasma concentrations by radioimmunoassay. Catecholamine levels were assessed by high-pressure liquid chromatography (HPLC) with electrochemical detection. RESULTS: Following MT, arterial hypotension occurred along with a substantial PGI2 release. This was completely abolished by ibuprofen administration. Although plasma levels of 6-keto-PGF1 alpha (1133 (708) vs. 60 (3) ng/L, median (median absolute deviation), P = 0.0001, placebo vs. ibuprofen) remained significantly elevated, blood pressure was restored within 30 min after MT in the placebo group. At the same point in time plasma concentrations of TXB2 (164 (87) vs. 58 (1) ng/L, P = 0.0001), epinephrine (46 (33) vs. 14 (6) ng/L, P = 0.001), AVP (41 +/- (18) vs. 12 (7) ng/L, P = 0.0004), and active renin (27 (12) vs. 12 (4) ng/L, P = 0.001) were significantly higher in placebo-treated patients. CONCLUSION: Under combined general and epidural anesthesia arterial hypotension following MT due to endogenous PGI2 release is associated with enhanced release of AVP, active renin, epinephrine and thromboxane A2, presumably contributing to hemodynamic stability within 30 min after MT.

Abdomen↗