Biomedical subjects

S Ernst

Publications and source records attributed to S Ernst.

At least 19 recordsLinked to original sources

PubMed1999

Analysis of sperm chromosome complements before, during, and after chemotherapy.

Sperm chromosomal abnormalities were assessed in testicular cancer patients before, during, and after BEP (bleomycin, etoposide, cisplatin) chemotherapy (CT). Multicolor fluorescence in situ hybridization (FISH) analysis was employed to detect aneuploidy for chromosomes 1, 12, X, and Y, and diploidy. Sperm samples were cryopreserved and coded before analysis to facilitate "blind" analysis. Complete results at all time points was available for only one patient. A total of 60,400 sperm were analyzed: 20,004 before CT, 20,005 during CT, and 20,391 after CT. There was a significant increase in the frequency of 24,XY sperm during (0.33%) and post-CT (0.34%) compared to pre-CT (0.14%). This study suggests that there may be a significantly increased risk of chromosomal abnormalities in sperm of CT patients during and immediately post-CT, similar to that shown in animal models.

Adult↗

PubMed1999

Outcome and safety of transrectal US-guided percutaneous cryotherapy for localized prostate cancer.

OBJECTIVES: To assess the effectiveness and safety of ultrasound (US)-guided cryotherapy as a primary treatment for localized prostate cancer. MATERIALS AND METHODS: A prospective study of percutaneous transrectal US (TRUS)-guided cryotherapy was performed on 71 patients with T1-T3, N0, M0 prostatic cancer: 10 patients underwent two or more procedures. All cases were newly diagnosed and patients had no previous treatment for cancer. For all patients, TRUS biopsies were performed at 5-6 months. Patients were monitored at 6 weeks; 3, 6, 9, and 12 months; and twice yearly thereafter for prostate specific antigen (PSA) levels, complications, and clinical evidence of residual disease. RESULTS: Follow-up from 10 to 36 months was available for 70 of 71 patients; one patient died of unrelated disease. Initially, 10 of 69 patients had positive postcryotherapy biopsy results. After repeated treatment, nine of these 10 patients had negative biopsy results and one patient had no follow-up. Overall, 68 of 69 patients had negative biopsy results. At 1 year, 43 of 64 (67%) had an undetectable PSA level. Two patients had proven metastases. Complications include three cases with urethral sloughing requiring transurethral resection of the prostate (TURP). One patient had orchitis. Two patients had persistent incontinence, one as the result of a TURP. There was no death, acute serious morbidity, or fistula formation. Impotence was universal at 6 months, but many patients demonstrated late recovery. CONCLUSION: Cryoablation is an imaging-guided percutaneous intervention for prostate cancer that can safely yield disease-free status in a high percentage of patients with localized disease.

Adenocarcinoma↗

PubMed1998

Mass spectrometric and capillary electrophoretic investigation of the enzymatic degradation of heparin-like glycosaminoglycans.

Difficulties in determining composition and sequence of glycosaminoglycans, such as those related to heparin, have limited the investigation of these biologically important molecules. Here, we report methodology, based on matrix-assisted laser desorption ionization MS and capillary electrophoresis, to follow the time course of the enzymatic degradation of heparin-like glycosaminoglycans through the intermediate stages to the end products. MS allows the determination of the molecular weights of the sulfated carbohydrate intermediates and their approximate relative abundances at different time points of the experiment. Capillary electrophoresis subsequently is used to follow more accurately the abundance of the components and also to measure sulfated disaccharides for which MS is not well applicable. For those substrates that produce identical or isomeric intermediates, the reducing end of the carbohydrate chain was converted to the semicarbazone. This conversion increases the molecular weight of all products retaining the reducing terminus by the "mass tag" (in this case 56 Da) and thus distinguishes them from other products. A few picomoles of heparin-derived, sulfated hexa- to decasaccharides of known structure were subjected to heparinase I digestion and analyzed. The results indicate that the enzyme acts primarily exolytically and in a processive mode. The methodology described should be equally useful for other enzymes, including those modified by site-directed mutagenesis, and may lead to the development of an approach to the sequencing of complex glycosaminoglycans.

Carbohydrate Sequence↗

PubMed1998

Direct evidence for a predominantly exolytic processive mechanism for depolymerization of heparin-like glycosaminoglycans by heparinase I.

Heparinase I from Flavobacterium heparinum has important uses for elucidating the complex sequence heterogeneity of heparin-like glycosaminoglycans (HLGAGs). Understanding the biological function of HLGAGs has been impaired by the limited methods for analysis of pure or mixed oligosaccharide fragments. Here, we use methodologies involving MS and capillary electrophoresis to investigate the sequence of events during heparinase I depolymerization of HLGAGs. In an initial step, heparinase I preferentially cleaves exolytically at the nonreducing terminal linkage of the HLGAG chain, although it also cleaves internal linkages at a detectable rate. In a second step, heparinase I has a strong preference for cleaving the same substrate molecule processively, i.e., to cleave the next site toward the reducing end of the HLGAG chain. Computer simulation showed that the experimental results presented here from analysis of oligosaccharide degradation were consistent with literature data for degradation of polymeric HLGAG by heparinase I. This study presents direct evidence for a predominantly exolytic and processive mechanism of depolymerization of HLGAG by heparinase I.

Carbohydrate Sequence↗

PubMed1998

Phase 2 trial of moderately high dose single agent mitoxantrone in platinum and paclitaxel-refractory ovarian cancer.

In the human clonogenic assay, mitoxantrone possesses among the steepest dose-response curves of any cytotoxic agent against ovarian cancer. To test the potential clinical relevance of this observation, we conducted a phase 2 trial of moderately high dose single agent mitoxantrone (28 mg/m2 delivered every 3-4 weeks) along with granulocyte-macrophage colony stimulating factor (250 micrograms/m2/day beginning 24 h after mitoxantrone and continuing until neutrophil recovery) in 34 patients with clinically defined platinum and paclitaxel-refractory ovarian cancer. The major toxicity of treatment was severe neutropenia which was almost universal. However, there were no treatment-related infectious deaths. Significant cardiac toxicity was not observed. Five of 33 evaluable patients demonstrated objective evidence of a response to treatment (1 patient achieving a partial response of measurable tumor masses, 4 patients achieving a > or = 50% reduction in CA-125 antigen level), with a median duration of response of 3 months (range 2-5 months). We conclude that moderately high dose mitoxantrone has definite, although very limited, single agent activity in platinum and paclitaxel-refractory ovarian cancer. Unfortunately, as this regimen produces severe hematologic toxicity and response durations are short, it cannot be recommended for routine clinical use. The role of an even higher dose mitoxantrone schedule employed as a component of a high dose chemotherapy program with bone marrow or peripheral progenitor cell protection in the treatment of ovarian cancer remains to be defined.

Adult↗

PubMed1998

[Renal angiomyolipoma as a rare cause of retroperitoneal hemorrhage].

Angiomyolipomas are hamartomas that may be found sporadically or associated with tuberous sclerosis (M. Bourneville-Pringle). Clinically, this long-term asymptomatic tumor becomes evident as an acute retroperitoneal hemorrhage or by symptoms of a flank mass. Due to the high percentage of fat components in this tumor type, computed tomography is far superior to other radiological procedures. In view of two of our own case reports, the therapeutic strategies are discussed, paying regard to the actual literature in this field.

Adult↗

PubMed1998

[Complications of CT guided lumbar sympathectomy: our own experiences and literature review].

AIM: To review the complications of CT guided lumbar sympathicolysis (CTLS) on the basis of our own experience and the available literature. METHODS: 241 CTLS were performed by a standard technique according to Haaga's method. Clinical follow-up revealed 4 serious complications; these were analysed and compared with published cases. RESULTS: Amongst our patients there were three fibrotic ureter stenoses and one retroperitoneal abscess. Analysis of the serious complications described in the literature indicates that introduction of CT guided lumbar sympathicolysis has reduced the severity and frequency of complications as compared with surgical and "blind" procedures. With CTLS, no deaths due to the procedure have been reported in the literature. The results indicate that damage to the ureters can be caused by substances used for the neurolysis. CONCLUSION: Provided certain safeguards are obeyed, CTLS is a very save treatment. However damage to the ureter may follow even when the procedure was technically satisfactory. Therefore, sonographic control of the kidneys after three months is recommended.

Abscess↗

PubMed1998

Use of dexamethasone and granisetron in the control of delayed emesis for patients who receive highly emetogenic chemotherapy. National Cancer Institute of Canada Clinical Trials Group.

PURPOSE: To evaluate the roles of granisetron and dexamethasone for emesis control on days 2 through 7 after the administration of cisplatin in doses of 50 mg/m2 or greater to patients who had not previously received chemotherapy. PATIENTS AND METHODS: Four hundred thirty-five eligible and assessable patients were randomized to one of two arms in a double-blind fashion: arm A; granisetron 3 mg intravenous (i.v.) plus dexamethasone 10 mg i.v. prechemotherapy followed by granisetron 1 mg orally at 6 and 12 hours, then granisetron 1 mg orally and dexamethasone 8 mg orally twice daily on days 2 through 7 (219 patients); arm B; as in arm A but with placebo substituted for granisetron on days 2 through 7 (216 patients). All patients completed diaries in which episodes of emesis and severity of nausea were recorded. RESULTS: The addition of granisetron on days 2 through 7 had no discernable impact on nausea and vomiting during this period. CONCLUSION: The administration of a 5-hydroxytryptamine3, receptor (5-HT3) antagonist, in this case granisetron, after 24 hours conferred no benefit. This negative result needs to be assessed in light of conflicting literature, but at present it does not appear that the routine use of these drugs in this setting is justified.

Antiemetics↗

PubMed1998

Economic evaluation of chemotherapy with mitoxantrone plus prednisone for symptomatic hormone-resistant prostate cancer: based on a Canadian randomized trial with palliative end points.

PURPOSE: To evaluate the economic consequences of the use of chemotherapy in patients with symptomatic hormone-resistant prostate cancer (HRPC) in the context of a previously published Canadian open-label, phase III, randomized trial with palliative end points. PATIENTS AND METHODS: The trial randomized 161 patients to initial treatment with mitoxantrone and prednisone (M + P) or to prednisone alone (P) and showed better palliation with M + P. There was no significant difference in survival. A detailed retrospective chart review was performed of resources used from randomization until death of 114 of 161 patients enrolled at the three largest centers: these included hospital admissions, outpatient visits, investigations, therapies (which included all chemotherapy and radiation), and palliative care. Cancer center and community hospital costs were calculated by using the hotel approximation method and case costing from the Ontario Case Cost Project, respectively. Cost-utility analysis was performed by transforming the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 global quality-of-life item measured every 3 weeks on trial to an estimate of utility, and extending the last known value through to death or last follow-up. RESULTS: The mean total cost until death or last follow-up by intention-to-treat was M + P CDN $27,300; P CDN $29,000. The 95% confidence intervals on the observed cost difference ranged from a saving of $9,200 for M + P (with palliative benefit) to an increased cost of $5,800 for M + P. The major proportion of cost (M + P 53% v P 66%; CDN $14,500 v $19,100) was for inpatient care. Initial M + P was consistently less expensive in whichever time period was used to compare costs. Cost-utility analysis showed M + P to be the preferred strategy with an upper 95% confidence interval for the incremental cost-utility ratio of CDN $19,700 per quality-adjusted life-year (QALY). CONCLUSION: A treatment that reduces symptoms and improves quality of life has the potential to reduce costs in other areas. Economic factors should not influence the clinical decision as to whether to use M + P in a symptomatic patient.

Canada↗

PubMed1998

Proton MR spectroscopy in infants with cerebral energy deficiency due to hypoxia and metabolic disorders.

PURPOSE: To investigate the similarities and differences of cellular energy deficiencies due to asphyxia and to impaired oxidative phosphorylation caused by enzyme deficiencies using localized 1H-MR spectroscopy of the brain. MATERIAL AND METHODS: In 35 neonates and infants with a postconceptional age of 36.4-153 weeks, 1H-MR spectra were obtained from the basal ganglia. Of the 35 children, 14 served as a control group, 12 suffered from hypoxic-ischemic disease (HIE), and 9 had congenital enzymatic disorders. RESULTS: Eleven of the 12 children with HIE showed low N-acetyl aspartate (NAA) to trimethylamine (TMA) ratios, indicating neuronal damage. Lactate (Lac) to TMA ratios correlated with the HIE grade. Children with congenital disorders of energy metabolism had NAA/TMA ratios ranging from severely decreased to normal, but 7 of the 9 had high Lac signals, even in brains with normal NAA/TMA. CONCLUSION: High Lac/TMA even with normal NAA/TMA in children with enzyme deficiencies, in contrast to Lac/TMA that correlates with clinical grade and low NAA/TMA in asphyxic children, hints at different mechanisms of cell damage in the two disease groups.

Aspartic Acid↗

PubMed1998

Calcitonin gene-related peptide mediates the protective effect of sensory nerves in a model of colonic injury.

Recently we demonstrated that sensory denervation with the neurotoxin capsaicin worsened the inflammation in an acute and chronic model of experimental colitis, which suggests a protective role of sensory nerve fibers during gut inflammation. Because we could demonstrate that sensory neuropeptides like Calcitonin gene-related peptide (CGRP) and substance P (SP) are released from sensory nerve fibers during intestinal inflammation, both are strong candidates as mediators for the protective effect of sensory neurons. In this study we investigate the role of CGRP and SP during experimental colitis in the rat by use of receptor antagonists against CGRP (CGRP 8-37, 1 microg/h continuous subcutaneous infusion), SP (RP67580, a NK-1 receptor antagonist, 3 mg/kg i.p.) and an immunoneutralizing CGRP-antibody. A mild colitis was induced by a rectal enema containing trinitrobenzenesulfonic acid. The severity of inflammation increased markedly after 7 days in the CGRP receptor antagonist and CGRP-antibody group compared with the vehicle group as determined by a macroscopic damage score (10.4 +/- 1.2 and 9.6 +/- 1.6 vs. 6.2 +/- 2.1) by a histologic ulceration score (82 +/- 8% and 73 +/- 6% vs. 42 +/- 23%) and by myeloperoxidase activity (19.2 +/- 6.8 and 18.1 +/- 5.9 vs. 8.6 +/- 5.3 U/mg tissue protein), respectively. Treatment with the specific SP receptor antagonist did not significantly alter the severity of colitis at 7 days compared with the control group. These data suggest that CGRP exerts mucosal protection during chronic experimental colitis.

Animals↗

PubMed1998

Nonfluoroscopic endocardial catheter mapping of atrial fibrillation.

The treatment of drug-refractory atrial fibrillation (AF) remains one of the unsolved problems in cardiology. Surgical interventions have demonstrated that AF can be prevented by multiple incisions within both atria. Recently, this strategy has been translated into a catheter procedure. So far, the ablation approach is not based on individual electrophysiologic data, but constitutes only an anatomic approach. Further insight into the spatial and temporal distribution of the local electrograms during AF is needed. Electroanatomic maps acquired by sequential mapping over 45 seconds at each site during AF in six patients with paroxysmal AF were analyzed off-line. Electrograms were sampled at a mean of 36 +/- 12 sites in the left atrium of each patient. A total of 217 sites were sampled, of which 27.3% (59) represented type A (regular) AF, 9.7% (21) represented type B (totally irregular), and 63.1% (137) represented type C (mixture of type A and B) electrograms. The distribution was analyzed in 20 different segments of the left atrium, and a significantly higher incidence of type A electrograms was found in area 3 (upper lateral pulmonary vein) than at all other sites (P < 0.005). This observation needs further confirmation before any conclusion with regard to catheter ablation can be drawn, particularly because the analysis was based on bipolar recordings from a 4-mm tip electrode.

Aged↗

PubMed1998

Effectiveness of megestrol acetate in patients with advanced cancer: a randomized, double-blind, crossover study.

PURPOSE: To evaluate the effect of megestrol acetate at a lower dose than previously investigated on the symptoms of cachexia in patients with advanced cancer. METHODS: A total of 84 patients with advanced, solid tumours not responsive to hormone therapy were enrolled in this double-blind, crossover study. During phase 1, patients were randomly assigned to receive megestrol acetate (160 mg 3 times daily) for 10 days or placebo. During phase 2, after a 2-day washout period, patients received the alternate treatment for 10 days. Patients underwent daily assessments of activity, nausea, appetite and well-being by means of a visual analogue scale (VAS). In addition, nutritional status (weight, tricep skinfold measure, arm muscle circumference), energy intake, fatigue (Piper Fatigue Scale) and quality of life (Functional Living Index-Cancer [FLIC]) were assessed. RESULTS: Among the 53 evaluable patients megestrol acetate resulted in a significant improvement in appetite (p = 0.005), activity (p = 0.007) and well-being (p = 0.03). There was no significant change in the intensity of nausea, nutritional parameters, energy intake or FLIC scores. There was a significant improvement in 2 of the 3 factors measured by the Piper Fatigue Scale and in the overall fatigue score. Upon completion of the study, while still blind to the treatment condition, 30 patients indicated that they felt better overall after megestrol, 15 said they felt better after placebo, and 10 indicated no preference (p = 0.001). CONCLUSION: Treatment with megestrol acetate results in rapid and significant improvement of symptoms in terminally ill patients at lower doses than previously reported. The effects are not secondary to nutritional changes. The FLIC quality-of-life questionnaire was unable to detect these changes.

Adult↗

PubMed1997

[99mTc-MDP-SPECT for detection of subclinical mandibular infiltration of squamous epithelial carcinoma].

UNLABELLED: A prospective study was performed to compare the sensitivity and accuracy of ultrasound (US), computed tomography (CT), and single photon emission computed tomography (SPECT) as a bone scan to detect subclinical invasion of the mandible by squamous cell carcinoma of the oral cavity and floor of mouth. METHODS: The present study reports data on 35 patients with squamous cell carcinoma of the oral cavity. SPECT, mandibular orthopantomography (OPG), US, CT and magnetic resonance imaging (MRI) were performed as well as histologic examination of resected mandibles. Transverse slices of 12 mm thickness were reconstructed for SPECT and semi-quantitative assessment of radionuclide uptake was performed with a scoring system based on comparisons of tracer uptake in the mandible to that in an unaffected part of the mandible. Lesion to non-lesion count ratios in the mandible in 3 h SPECT images were calculated. OPG, US and CT were evaluated for comparison. RESULTS: In 12/35 patients, histologic examination showed carcinoma infiltrating mandibular bone. SPECT correctly predicted mandibular invasion in 11/12 cases, with no false-positive results. CT detected correctly 3/12 lesions, while OPG and ultrasound each demonstrated 2/12 tumors. CONCLUSION: Bone SPECT was found to provide an accurate means for assessing tumor invasion to the mandible by intraoral squamous cell carcinoma. As a complementary study to one of the other imaging modalities it was shown to have a high specificity, indicating that it should be performed routinely in patients with suspect mandibular bone involvement by causes.

Adult↗

PubMed1997

Chromosomal abnormalities in sperm from testicular cancer patients before and after chemotherapy.

Sperm chromosome abnormalities were assessed in testicular cancer patients before and after treatment with BEP (bleomycin, etoposide, cisplatin). The frequencies of disomy for chromosomes 1, 12, X, Y and XY were assessed along with diploid frequencies and sex ratios by multicolour fluorescence in situ hybridization (FISH). For each cancer patient, a minimum of 10,000 sperm was assessed for each chromosome probe before and after chemotherapy (CT). Data was analysed "blindly" by coding the slides. A total of 161097 sperm were analyzed, 80,445 before and 80,642 after treatment. The mean disomy frequencies were 0.11% pre-CT vs 0.06% post-CT for chromosome 1, 0.18% vs 0.15% for chromosome 12, 0.10% vs 0.9% for the X chromosome, 0.13% vs 0.10% for the Y chromosome and 0.25% vs 0.20% for XY sperm. There was no significant difference in the frequency of disomy pre-CT vs post-CT for any chromosome except that chromosome 1 demonstrated a significant decrease after CT. The "sex ratios" and frequency of diploid sperm were also not significantly different in pre and post-CT samples with 50.2% X-bearing sperm pre-CT and 50.5% X post-CT and 0.14% diploid sperm pre-CT vs 0.15% diploid sperm post-CT. There was no significant donor heterogeneity among the cancer patients. None of the values in the cancer patients differed significantly from 10 normal control donors. Thus our study suggests that BEP chemotherapy does not increase the risk of numerical chromosomal abnormalities in human sperm.

Adult↗

PubMed1997

Cancer pain emergencies: a protocol for management.

Cancer is often associated with chronic pain, which can be managed by established algorithms. Cancer is also occasionally associated with sustained episodes of excruciating pain (cancer pain emergencies) that require rapid application of powerful analgesic strategies in a manner that is distinct from chronic pain management techniques. To clarify the utility of rapid opioid dose escalation in this setting, we reviewed the management of ten cancer pain emergencies in nine patients. After initial assessment, all patients were managed according to a protocol whereby intravenous boluses of opioid are administered with rapid upward titration until an effective analgesic dose is found. Using this technique, all patients had relief of their excruciating pain after a mean of 89 min (range, 4-215 min). No patient demonstrated evidence of significant toxicity. We conclude that repeated intravenous boluses of an opioid, doubling the dose every 30 min until analgesia is achieved, is effective and safe management of cancer pain emergencies. Validation of this protocol is required.

Adult↗

PubMed1997

Reoperative aortic root surgery late after use of histo-acryl.

Cardiovascular reoperations after the use of histo-acryl are extremely rare. A patient is described, who underwent an aortic root replacement according to Bentall's technique, for a postdissectional aneurysm. At that time, to achieve hemostasis, histo-acryl adhesive was applied and a Cabrol's fistula was created. Fourteen years later, a recurrent 'false', aneurysm had developed and the fistula had a hemodynamically significant left-right shunt. At reoperation, the composite graft was replaced by a cryopreserved aortic root allograft with long coronary arteries. To our knowledge, this is the first report of a cardiovascular reoperation after previous use of histo-acryl. This patient also merits attention as to the fact that it illustrates a failure of a modified Cabrol's procedure.

Adult↗

PubMed1997

[31P-MR spectroscopy of the human liver--the spectral indications of lymphoma infiltration].

PURPOSE: To evaluate whether phosphorus magnetic resonance spectroscopy (31P-MRS) enables a non-invasive detection of liver involvement in systemic diseases like Hodgkin's lymphoma. MATERIALS AND METHODS: Using a clinical 1.5 Tesla whole-body MR system image-guided localised phosphorus MR spectra from the anatomically defined volumes of interests were measured. A combination of surface coil, adiabatic excitation pulse and modified image-selected in vivo spectroscopy (ISIS)-sequence was applied. The spectroscopy data were evaluated quantitatively with a time-domain fit programme using non-linear optimisation algorithms to quantify peak areas. After establishment of the examination protocol, 22 healthy volunteers and 13 patients with suspected lymphoma infiltration of the liver were examined. RESULTS: Liver spectra of patients suffering from lymphoma infiltration differed significantly from spectra of persons with normal liver: 1. The peak area ratio of phosphomonoesters (PME) to beta-NTP was elevated in all patients with histologically confirmed liver lymphoma. 2. Patients suffering from Hodgkin's disease with specific or unspecific liver infiltration (n = 7) could be differentiated from patients without liver involvement. In case of infiltrated liver, the peak area ratio PME to beta-NTP was increased, and the pH value was shifted to lower values. Unambiguous differentiation between non-specific (n = 3) and specific (n = 4) infiltration of the liver was not possible. 3. In patients after cytostatic treatment (n = 3), an increase of the peak area ratio of inorganic phosphate to beta-NTP was observed. CONCLUSIONS: Our preliminary results indicate that 31P-MRS can yield pointers to liver involvement in patients with systemic diseases such as Hodgkin's disease, which may be hardly detected by imaging methods.

Adolescent↗