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H Engler

Publications and source records attributed to H Engler.

At least 19 recordsLinked to original sources
PubMed2002

Short-term effects of atorvastatin on C-reactive protein.

AIM: To study the short-term effect of atorvastatin on C-reactive protein (CRP) in patients with or at risk for coronary heart disease. METHODS AND RESULTS: One hundred and fifty-five randomly selected patients from the SWiss Intervention Trial for lowering CHolesterol (SWITCH) were assessed for high sensitivity CRP, total cholesterol, LDL-cholesterol, HDL-cholesterol and triglycerides at baseline, and after 1 and 3 months of treatment with atorvastatin at various doses to reach pre-defined lipid target values. The median decrease of cholesterol was 28% after 1 month and 35% after 3 months. LDL-cholesterol was decreased by 37% and 45%, HDL-cholesterol was increased by 7% and 8%, respectively. Patients with a low CRP baseline concentration (lowest quartile <1.34 mg. l(-1)) displayed no significant change, whereas patients in the other quartiles showed a significant decrease, of 22% to 40% (P -value <0.05 to <0.001) at 1 month and of 32% to 36% after 3 months compared to baseline. The decrease in CRP lowering was thus fully established by 1 month and this response was independent of lipid and lipoprotein changes as well as atorvastatin doses. CONCLUSION: Atorvastatin significantly decreases CRP concentrations after 4 weeks of therapy. These results may be important with respect to the early benefit of statin therapy.

Anticholesteremic Agents↗
PubMed2001

Positron emission tomography (11)C-methionine and survival in patients with low-grade gliomas.

BACKGROUND: Considerable numbers of patients with low-grade gliomas experience an early malignant course and may benefit from aggressive treatment. These patients are difficult to identify using established prognostic factors. A retrospective study was performed to determine whether the (11)C-methionine uptake in tumor is a survival factor in adult patients with supratentorial gliomas classified as World Health Organization Grade 2. METHODS: The authors identified 89 patients with histologically confirmed low-grade gliomas in whom an (11)C-methionine positron emission tomography (PET) scan had been performed as part of the diagnostic tumor investigation from 1983 to 1998. Clinical data were collected, and the PET scans were re-evaluated according to a fixed protocol. The (11)C-methionine uptake in the tumor and relevant clinical parameters were entered into univariate and multivariate survival analyses. RESULTS: At the end of the study, 49 patients (55.1%) had died. The median overall survival was 5.7 years. Low methionine uptake was significantly favorable in the multivariate survival analysis (P = 0.04) along with oligodendroglioma (P = 0.003). In the histologic subgroups, (11)C-methionine uptake was an important survival factor among patients with astrocytomas (P = 0.05) and oligodendrogliomas (P = 0.03). Tumor resection was a favorable prognostic factor in patients with high methionine uptake (P = 0.01) but not in patients with low uptake. CONCLUSIONS: Baseline (11)C-methionine PET is a prognostic indicator in patients with low-grade gliomas. The results imply that PET is a valuable tool in the clinical management of these patients and may assist in the selection of patients for therapy.

Adult↗
PubMed2001

Re-engineering adenovirus regulatory pathways to enhance oncolytic specificity and efficacy.

Replicating adenoviruses may prove to be effective anticancer agents if they can be engineered to selectively destroy tumor cells. We have constructed a virus (01/PEME) containing a novel regulatory circuit in which p53-dependent expression of an antagonist of the E2F transcription factor inhibits viral replication in normal cells. In tumor cells, however, the combination of p53 pathway defects and deregulated E2F allows replication of 01/PEME at near wild-type levels. The re-engineered virus also showed significantly enhanced efficacy compared with extensively studied E1b-deleted viruses such as dl1520 in human xenograft tumor models.

Adenoviridae↗
PubMed2001

Interferon alpha2b gene delivery using adenoviral vector causes inhibition of tumor growth in xenograft models from a variety of cancers.

A recombinant adenovirus expressing human interferon alpha2b driven by the cytomegalovirus promoter, IACB, was shown to produce and secrete biologically active protein in vitro and in vivo. Intravenous administration of IACB in Buffalo rats resulted in circulating levels of biologically active human interferon at 70,000 international units/mL for up to 15 days. Distribution of interferon protein after IACB administration was different from that seen with the subcutaneous delivery of interferon protein. Higher levels of interferon protein were observed in liver and spleen after IACB delivery compared to protein delivery. The antitumor efficacy of IACB, as measured by suppression of tumor growth, was tested in athymic nude mice bearing established human tumor xenografts from different types of human cancer. Subcutaneous tumors most responsive to the intratumoral administration of IACB ranked as U87MG (glioblastoma) and K562 (chronic myelogenous leukemia), followed by Hep 3B (hepatocellular carcinoma) and LN229 cells (glioblastoma). Intravenous administration of IACB in animals bearing U87MG or Hep 3B xenografts was also effective in suppressing tumor growth, although to a lesser extent than the intratumoral administration. IACB was also tested in a metastatic model in beige/SCID mice generated with H69 (small cell lung carcinoma) cells and was found to prolong survival in tumor-bearing animals. This suggested that interferon gene delivery can be effective in suppressing tumor growth in a wide variety of cells.

Adenoviridae↗
PubMed2001

Identification of polyamides that enhance adenovirus-mediated gene expression in the urothelium.

Adenovirus-mediated gene therapy of bladder diseases has been limited by the inability to transduce the urothelium successfully using adenoviral vectors. We have sought to identify agents that would increase adenovirus-mediated transgene expression in the bladder. We have utilized a rat model to screen compounds for their ability to enhance viral transgene expression in the rat bladder. Rats received intravesical administration of replication-deficient adenovirus (rAd) formulated in various agents, and transgene expression was evaluated after 48 h by determining the amount of lacZ expression in the luminal epithelium of the bladder. We report the identification of two different polyamides, each capable of dramatically increasing viral transgene expression in the bladder without causing detectable alteration of the umbrella cell layer of the urothelium. We have utilized a carcinogen-induced rat bladder tumor model to demonstrate that these polyamides are also capable of enhancing viral transgene expression in tumor tissue. The identification of these polyamides potentiates the use of adenovirus-mediated gene therapy for the treatment of superficial bladder cancer or other bladder diseases.

Adenoviridae↗
PubMed2001

Alterations of lipolytic enzymes and high-density lipoprotein subfractions induced by physical activity in type 2 diabetes mellitus.

OBJECTIVE: This study investigates the effects of regular moderate physical activity on lipolytic enzymes and plasma lipid concentration, particularly high-density lipoprotein cholesterol (HDL-C) subfractions, in patients with type 2 diabetes mellitus. DESIGN: Ten patients participated in a 3-month exercise programme without any changes in current medical therapy. The control group consisted of six patients who were matched with regard to sex, age, diabetes duration and diabetes therapy. RESULTS: Mean (+/- SE) physical activity in the intervention group increased from 70 +/- 21 to 220 +/- 28 min per week, which resulted in an increase in total HDL-C from 1.04 +/- 0.07 to 1.28 +/- 0.12 (P < 0.001). The HDL3-C subfraction increased from 0.71 +/- 0.08 to 0.86 +/- 0.08 mM (P = 0.01) with no significant changes in the HDL2-C subfraction (0.33 +/- 0.04 vs. 0.42 +/- 0.05). These changes were paralleled by an 85% increase in hepatic lipase (HL) activity, from 25.7 +/- 5.1 to 47.4 +/- 4.9 micromol x mL(-1) x h(-1) (P < 0.001) and a 45% increase in lipoprotein lipase (LPL) activity, from 16.8 +/- 3.0-24.3 +/- 2.7 micromol x mL(-1) x h(-1) (P = 0.01). Lecithin-cholesterol acyl-transferase (LCAT) activity increased by 32%, from 156 +/- 26 to 206 +/- 32 nmol x mL(-1) x h(-1) (P < 0.001). In the control group there were no significant changes in any of the variables assessed. CONCLUSIONS: Regular moderate physical activity in patients with type 2 diabetes led to an overall increase in HL, LPL, and LCAT. HL showed a more pronounced increase than LPL and LCAT. The changes in lipolytic and transferase enzyme pattern resulted in a significant increase of plasma HDL-C, mainly of the HDL3-C subfraction.

Adult↗
PubMed2000

3. Utility of PET and 11C-Methionine in the Paediatric Brain Tumors.

Purpose: The aim of the study was to examine the utility of PET with 11C-Methionine in diagnosis and evaluation of the treatment efficacy in childhood brain tumors.Methods: 16 PET-studies were performed in 11 children, 4-17years old, 3 boys and 8 girls, with brain tumors or tumor suspicion. Reasons for PET-study were an unclear diagnosis of tumor (7 cases), treatment efficacy definition (5 cases) and identification of tumor recurrence (3 cases). Studies were performed after i.v. injection of 11C-Methionine (6-9 MBq/kg). MRI or CT of brain was done before the PET-study in all patients. Diagnosis was confirmed by clinical follow-up or biopsy.Results: In 2 of 7 patients with suspicion of brain tumor no areas with pathological uptake of 11C-Methionine were found. In a patient with unclear tumor a benign process (ependimoma) was revealed that allowed avoiding a biopsy. A benign tumor detection in 2 patients with malignancy suspicion considerably affected treatment tactics. In 2 patients supposed benign growth was confirmed. In 2 of 3 patients with question of recurrence after surgery or radiotherapy and inconclusive MRI and CT picture malignant growth was found and in 1 patient was rejected. Repeated PET-studies in 2 patients with prolactinoma during therapy allowed prompt (within a few days) control of tumor response.Conclusion: The assessment of tumor metabolic activity in paediatric oncological practice using PET with 11C-Methionine is a reliable method in the correct indication of brain tumor origin and in prompt evaluation of treatment efficacy and control of recurrence.

Journal Article↗
PubMed2000

6. 18F-FDG Whole Body Positron Emission Tomography (PET) in the Detection of Unknown Primary Tumors.

Purpose: To evaluate the utility of FDG-PET in detecting primary tumors in patients with metastatic disease from unknown primary tumors.Methods: 12 patients with metastases from unknown origin after unsuccessful conventional diagnostic procedures were studied. 5 had lymph node metastases (2 axillary, 2 cervical, 1 mediastinal), 3 multiple metastases, 1 in the lung, 1 in the cava vein, 1 in the brain and 1 in adrenal glands. Patients received 400MBq FDG intravenously, and whole body images were acquired 60 min. after injection with an ECAT EXACT HR+. PET results were compared with histological and clinical findings.Results: All but one metastatic lesion was identified by PET. Additional metastases were visualized in 4 patients. In one helped to guide biopsy for histological diagnosis. In 4/11 patients FDG-PET did not reveal lesions suspected to be primary tumor. FDG-PET identified primary tumor in 8/11 patients (breast: 2, pancreas: 2, base of tongue: 1, adrenal gland: 1, lung: 1, stomach: 1). In 4 of them (33% of total) primary tumor was confirmed either histologically or by the clinical evolution (breast: 2, lung: 1, pancreas: 1). In 1 patient FDG-PET was false positive (base of tongue). 3 patients positive FDG-PET have not yet been confirmed. FDG-PET influenced therapeutic procedures in 4 patients (33% of total). 2 underwent surgery (breast), 1 received specific chemotherapy (lung) and 1 palliative chemotherapy (pancreas).Conclusions: Our preliminary results suggest that FDG-PET is a non-invasive technique useful in the detection of unknown primary tumors, can influence in selecting appropriate therapeutic management and could guide biopsies for histologic analysis.

Journal Article↗
PubMed2000

Gender differences in Parkinson's disease symptom profile.

Gender symptom differences were studied in 948 subjects with Parkinson's disease (PD) using a questionnaire covering the most common symptoms associated with PD at debut (SP-1) and at present (SP-2). The symptoms most frequently reported by both genders were: tremor, fumblingness, writing problems, rigidity and fatigue. At SP-1 females reported neck-pain and low back pain more frequently than males. At SP-2 subjects reported an increased number of symptoms. The following symptoms were more frequent among males than females: writing difficulties, fumblingness, gait problems, speech problems, increased flow of saliva, lack of initiative. Sleep problems were common in both sexes with inability to turn in bed and calf muscle cramps in a high percentage. A majority of female subjects find their symptoms (e.g. depression) constantly distressing. Although depression is not one of primary reported symptoms (36%) attention is called for, due to the problem with compliance to treatment regimes. About 30% do not report having tremor and rigidity. This study indicates the usefulness of a symptom profile instrument capable of capturing the many symptoms involved in PD. Such an instrument could be used to detect apparent mistakes in medication and thereby increase the function and quality of life for the individual.

Aged↗
PubMed1999

Social stress, dominance and blood cellular immunity.

The impact of chronic social coexistence on distribution and function of blood immune cells was examined in Long Evans rats. At the beginning of a 7 day period of chronic coexistence (confrontation), a wall was removed between two neighboring cages each consisting of a male-female pair. Winner and loser males were classified based on differences in their defensive behavior. On day 2 and 7 of confrontation, losers showed reductions in numbers of blood CD4 and CD8 T cells as well as profound suppression of in vitro NK activity and lymphocyte (LYM) proliferation. Numbers of granulocytes (GRAs) were more than doubled. Winner males showed similar immunological alterations only on day 2 of confrontation. On day 7 most changes were reversed. The persistent changes in loser males may reflect a less favorable state for effective immune response.

Animals↗
PubMed1999

Biochemical markers of bone turnover in patients with thyroid dysfunctions and in euthyroid controls: a cross-sectional study.

Hyperthyroidism is associated with reduced bone mineral density. Conflicting data exist regarding the effects of thyroxine therapy on bone metabolism. The aim of the present study was to assess changes in markers of bone turnover in thyroid dysfunction. A total of 28 patients with overt hyperthyroidism, eight patients with suppressed TSH levels (thyroid hormones within the euthyroid range, no T4 therapy), 25 euthyroid and four hypothyroid patients were included in the present study. Hyperthyroidism resulted in increased bone metabolism, as reflected by increased bone resorption and bone formation parameters. No significant differences in mean levels between patients with TSH supression and those with euthyroidism could be observed; however, a higher frequency of elevated urinary PYD- and DPD excretion rates were noted in patients with TSH suppression. Regression analysis revealed highly significant correlations between bone resorption markers and thyroid parameters, suggesting, that even a mild thyroid hormone excess may lead to an increase in bone resorption. In subjects with suppressed TSH levels and peripheral thyroid hormone levels within the euthyroid range, elevated bone resorption markers point to subclinical hyperthyroidism, if other reasons for an increase in bone turnover rates can be excluded.

Adult↗
PubMed1999

Ethanol improves adenovirus-mediated gene transfer and expression to the bladder epithelium of rodents.

OBJECTIVES: Replication deficient adenoviral vectors (rAds) are used as gene delivery systems that can efficiently transduce a variety of tissues and may be appropriate vectors to develop gene therapeutics for many urologic applications. However, the bladder epithelium has been shown to be highly resistant to transgene expression after intracystic administration. A potential explanation for this low gene transfer efficiency may be the protective structure of the urothelium. Since this protective barrier can be disrupted by organic solvents, we assessed whether ethanol co-administration can enhance adenovirus-mediated transgene expression. METHODS: Normal and bladder tumor-bearing rats received a single intracystic administration of rAd encoding beta-galactosidase (rAd-beta gal) or p53 (rAd-p53). rAd was administered in a saline solution or in solutions with increasing concentrations of ethanol. Transgene expression was evaluated in the bladder tissues. RESULTS: A dramatic increase in urothelial beta-galactosidase transgene expression was achieved by rAd-beta gal administered in a 22% ethanol solution. Transgene expression was enhanced in normal urothelium and in superficial bladder tumors. p53 transgene expression was similarly enhanced. CONCLUSIONS: Co-administration of 22% ethanol enhanced local rAd-mediated transgene expression in the normal and neoplastic bladder epithelium in rodents. Improvement of rAd-mediated transgene expression is progress toward local gene delivery to the urothelium and may enable local gene therapy for superficial bladder cancer or other bladder diseases.

Adenoviridae↗
PubMed1999

Patients with morbid obesity don't get life-saving bone marrow transplants.

When the patient, a registered nurse, was surgically treated for morbid obesity she initially lost 54.5 kg. Approximately 2 years after gastric bypass, she received a diagnosis of chronic myelogenous leukemia and subsequently underwent a successful allogenic bone marrow transplant (BMT). When her surgical history was taken at the transplant facility, the significant weight loss and gastric bypass were discussed. She was informed that at 140 kg, she would not have been eligible nor considered a candidate for transplant. A search of the literature and a survey of other facilities confirmed this view as typical. The reasons cited were that the chemotherapy dosage required for the morbidly obese weight level would cause fatal organ damage as opposed to organ-sparing dosages, which would not eradicate all leukemic cancer cells. An additional general view was that the morbidly obese could not survive the rigors of the transplant preoperative regimen. This patient had an uneventful recovery and remains disease-free today, 3 years after BMT and 5 years after gastric bypass, with a sustained total weight loss of 73 kg.

Body Weight↗
PubMed1998

Effects of acute and chronic social stress on blood cellular immunity in rats.

The study compares the impact of acute and chronic social confrontation on aspects of blood cellular immunity in Long-Evans intruder rats. An adult male was introduced for either 2 h or 48 h into a male-female resident group, which resulted in fights for dominance. Thirty-eight of the 42 intruders became losers. For immunologic measurements, blood samples were taken from the intruders before confrontation (baseline) and 2 h or 48 h after the beginning of confrontation. Two h of confrontation resulted in increased granulocyte (+65%) and decreased lymphocyte numbers (-60%), as well as in differential reductions in CD4, CD8, and B cell numbers. CD4/CD8 and T/B ratios were elevated. T cell responsiveness to ConA was markedly suppressed in proliferation assays using either whole blood (-90%) or PBMC (-50%). The direction of changes in leukocyte and lymphocyte subsets after 48 h resembled in many aspects the 2 h changes, although with lower magnitude. In contrast to acute stress, a lowered T/B cells ratio and unaffected CD4/CD8 ratio was determined after 48 h. Proliferative response of T cells was lowered by about 25% in the whole blood assay; but unaffected in the PBMC assay. Significant correlations were found between the amount of submissive behavior displayed by the losers and several immunologic measures after 2 h of confrontation. The data suggest that acute and chronic stressful conditions may not necessarily result in similar effects on immune functioning. This should be considered when evaluating the biologic and evolutionary consequences of social stress-induced immune alterations.

Acute Disease↗
PubMed1998

High incidence of adeno- and polyomavirus-induced hemorrhagic cystitis in bone marrow allotransplantation for hematological malignancy following T cell depletion and cyclosporine.

Nine of 56 (20% actuarial) patients receiving a T cell-depleted, HLA-identical sibling BMT for hematological malignancy developed hemorrhagic cystitis (HC) 15-368 days post BMT. Hematuria was severe and prolonged (median duration 18 days). In eight patients (89%), a viral etiology was confirmed (four adenovirus, four polyomavirus). HC was associated with significant morbidity, with all patients requiring continuous bladder irrigation and transfusion support for blood loss and thrombocytopenia. HC occurring before day 100 was significantly associated with a reduction in long-term survival: 1/7 (14.3%) patients developing HC before day 100 became long-term survivors vs 21/49 (42.8%) without HC by day 100 (P = 0.034). In univariate analysis, HC was associated with a diagnosis of multiple myeloma (P = 0.02). There was a trend towards a higher incidence of HC in patients reactivating cytomegalovirus (CMV) compared with those remaining CMV negative (18.4 vs 5.5% respectively, P = 0.17). HC was not associated with graft-versus-host disease, or with the transplant dose of CD34+ progenitors or CD3+ cells, patient age or sex. Life-threatening, viral-induced HC and the unusually high incidence of adenovirus-induced HC may have been caused by immune deficiency associated with T cell depletion in this series.

Adenoviridae Infections↗
PubMed1998

Effect of thyroid hormones on Lp(a) and lipid metabolism.

The effect of thyroid hormones on lipoprotein(a) plasma concentrations and the other parameters of lipoprotein metabolism was studied in 158 patients with thyroid dysfunction and in 37 euthyroid controls (cross-sectional study). Multiple regression analysis revealed that 65.5% of the variability in lipoprotein(a) levels were predicted by changes in lipoprotein(a) phenotypes (60.5%), thyrotropin (3.5%), and age (0.8%). The lipid parameters, however, showed no significant effect on lipoprotein(a). A subgroup analysis on samples from patients with large lipoprotein(a) isoforms showed that 28% of the variability in lipoprotein(a) concentrations could be explained by changes in thyroid function (19.1%), age (6.5%) and triglycerides (3.5%). Much stronger correlations were found between thyrotropin and total cholesterol, low density lipoprotein cholesterol or apolipoprotein B respectively (R2=0.951 for low density lipoprotein cholesterol, R2=0.801 for apolipoprotein B). Our data suggest that thyroid hormone is a significant modulator of lipoprotein(a) metabolism. However, different mechanisms are responsible for the change in lipoprotein(a) levels and for the decrease in total- and low density lipoprotein cholesterol levels.

Adult↗
PubMed1998

Diagnostic and prognostic value of biochemical markers in malignant bone disease: a prospective study on the effect of bisphosphonate on pain intensity and progression of malignant bone disease.

Seventy cancer patients with malignant osteolytic bone disease received pamidronate every three weeks for a maximum of six cycles. Bone resorption parameters, urinary calcium excretion, and pain parameters were assessed at baseline and throughout the study. At baseline, 80-95% of patients showed elevated urinary pyridinoline, deoxypyridinoline, Osteomark NTx and serum ICTP levels, whereas only 35% of patients had elevated urinary CrossLaps excretion rates. During bisphosphonate therapy, significant decreases in Osteomark NTx, CrossLaps and calcium excretion were observed, which were not related to the clinical outcome. The baseline levels of bone resorption markers were used to predict the probability of non-progressive bone disease or reduction in pain intensity during bisphosphonate therapy. Significant predictors of non-progressive bone disease were urinary pyridinoline and serum ICTP levels; significant predictors of reduction in pain intensity were urinary free deoxypyridinoline and serum ICTP levels. Our data indicate that serum ICTP levels predict significantly the response to bisphosphonate therapy in patients with advanced malignant osteolytic bone disease. CrossLaps did not predict the clinical outcome, but decreased significantly during bisphosphonate therapy. Our data demonstrate that the different bone resorption markers are reflecting different aspects of bone metabolism, and therefore differ in their diagnostic and prognostic properties.

Aged↗