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Biomedical subjects

T Zimmermann

Publications and source records attributed to T Zimmermann.

At least 37 records · Page 2Linked to original sources
PubMed2001

Successful treatment of aids related PML with HAART and cidofovir.

Progressive multifocal leukoencephalopathy (PML) is a progressive demyelinating infection of the central nervous system caused by the JC virus (JCV) in an advanced state of the acquired immunodeficiency syndrome (AIDS). Currently there are still no drugs with proven clinical efficacy against JCV, though highly active antiretroviral therapy (HAART) and the associated partial immune reconstitution have a beneficial effect on the survival time of AIDS-related PML. Various case reports have described an acceptable response under treatment with cidofovir which may be of particular benefit if HAART does not result in sufficient immune reconstitution. We report a patient with AIDS-related PML who improved under combined therapy with HAART and cidofovir. This suggests that the immediate combination of both drugs further improves the outcome of AIDS-related PML.

AIDS-Related Opportunistic Infections↗
PubMed2001

Independent HIV replication in paired CSF and blood viral isolates during antiretroviral therapy.

BACKGROUND: The goal of highly active antiretroviral therapy in HIV-infected patients is to reduce plasma viral load (VL) below quantifiable levels. Mutations associated with drug resistance within the HIV-1 genome can limit therapeutic success. Low VL implicates a low risk of emergence of resistant mutants. Whether there is divergent development of HIV strains in different biologic compartments is not understood. METHODS: The authors studied VL and the occurrence of mutations conferring resistance in viral genomes isolated from blood and CSF samples of 23 HIV-infected patients. They determined sequences of HIV-1 RNA by reverse transcriptase PCR amplification and direct sequencing. They measured resistance to antiretroviral drugs genotypically by detection of drug-related point mutations and VL by a branched-DNA assay. RESULTS: Amplification of HIV was successful even in patients with plasma or CSF VL below detection limit. VL was considerably lower in CSF as compared with blood (p < 0.0001). There was no correlation between CSF and plasma VL. The mutational pattern in viral copies derived from blood and CSF was not identical. Ten (9%) of the total number of 118 mutations associated with drug resistance occurred in blood isolates only; 14 (11%) were detected exclusively in CSF strains. CONCLUSION: There is evidence for viral replication at HIV RNA levels less than 50/mL. The results suggest divergent evolution of HIV-1 in different biologic compartments. The presence of resistant mutants in the CSF may escape regular diagnostic in blood. Therapeutic success may fail after adapting therapy to genotypic resistance patterns detected in one compartment only.

Adult↗
PubMed2001

Peripheral primitive neuroectodermal tumor: challenge for multimodal treatment.

The primitive neuroectodermal tumor (PNET) is an extremely aggressive soft tissue neoplasm that occurs in children and adolescents. We retrospectively reviewed our therapeutic experience with a multidisciplinary approach, combining surgery, chemotherapy, and radiation therapy. Treatment of PNET was carried out in compliance with the soft tissue protocol (CWS) from the German Society of Pediatric Oncology. Biopsy-proven diagnosis was followed by chemotherapy, which in all cases led to partial remission, allowing excision of the remainder of the tumor without mutilation. After excision, irradiation of the tumor site and two further sequences of chemotherapy were performed. When PNET of the paravertebral region caused symptoms of paralysis and immediate surgery was required, postoperative chemotherapy, a second-look operation, and irradiation were undertaken. Between 1986 and 1998 we treated 13 patients (median age 15 years). In five patients the PNET originated from the chest wall and in eight patients from the paravertebral and retroperitoneal region. Five patients died after 20 months on average, and the remaining eight patients are in full remission after 7, 16, 46, 55, 70, 74, 75, and 115 months, respectively. Close cooperation between surgeons and their pediatric and radiotherapy colleagues is obligatory when treating PNET. Chemotherapy as the first stage is mandatory to avoid a mutilating surgical procedure and intraoperative tumor cell dissemination.

Adolescent↗
PubMed2001

[Left ventricular diastolic function in pregnancy in patients with arterial hypertension. A prospective study with M-mode echocardiography and Doppler echocardiography].

INTRODUCTION: During pregnancy eminent cardiovascular changes occur. The aim of the following study was to investigate the course of hemodynamic parameters under increased volume load during pregnancy in women suffering from mild arterial hypertension. METHODS: Altogether 47 women (age: 25 +/- 4 years) with mild arterial hypertension detected during pregnancy underwent echocardiography at the 9th, 24th and 33rd week of gestation. Furthermore echocardiography was performed postpartum at weeks 1 and 8. The control group comprised 45 healthy pregnant women. In all patients left ventricular muscle mass index and systolic shortening fraction were measured. The following Doppler echocardiographic parameters were ascertained: peak early diastolic and peak late diastolic flow, VE/VA ratio, acceleration time, deceleration time and isovolumetric relaxation time. RESULTS: During pregnancy all patients had an increase of left ventricular muscle mass index and a decrease of fractional shortening. All patients developed a relevant diastolic dysfunction. While the control group developed signs of disturbed relaxation as reduction of peak early diastolic flow (0.89 +/- 0.07 versus 0.82 +/- 0.08 m/s*), VE/VA ratio and an increase of isovolumetric relaxation time (72 +/- 12 versus 123 +/- 7*) at the 33rd week of gestation (* p < 0.01), all pregnant women with mild arterial hypertension developed a diastolic dysfunction with signs of delayed relaxation already at the beginning of gestation. 26 pregnant women with arterial hypertension developed a restrictive diastolic filling pattern at 24 weeks of gestation. The other 21 pregnant women only showed restriction for a short time at the end of gestation. In healthy pregnant women, volume load results in a reversible physiologic left ventricular hypertrophia, a significant alteration of diastolic left ventricular function in terms of a disturbed relaxation pattern and a temporary decrease of systolic function. In comparison hypertensive pregnant women show a delayed relaxation at the beginning of pregnancy and 50% developed early signs of restrictive cardiomyopathy. These changes may predispose to critical complications during pregnancy.

Adult↗
PubMed2001

Kinesin-dependent movement on microtubules precedes actin-based motility of vaccinia virus.

Vaccinia virus, a close relative of the causative agent of smallpox, exploits actin polymerization to enhance its cell-to-cell spread. We show that actin-based motility of vaccinia is initiated only at the plasma membrane and remains associated with it. There must therefore be another form of cytoplasmic viral transport, from the cell centre, where the virus replicates, to the periphery. Video analysis reveals that GFP-labelled intracellular enveloped virus particles (IEVs) move from their perinuclear site of assembly to the plasma membrane on microtubules. We show that the viral membrane protein A36R, which is essential for actin-based motility of vaccinia, is also involved in microtubule-mediated movement of IEVs. We further show that conventional kinesin is recruited to IEVs via the light chain TPR repeats and is required for microtubule-based motility of the virus. Vaccinia thus sequentially exploits the microtubule and actin cytoskeletons to enhance its cell-to-cell spread.

3T3 Cells↗
PubMed2001

[Efficacy of elective lymph node dissection in malignant melanoma of the extremities and trunk. An analysis in view of the sentinel lymph node biopsy].

Elective lymph node dissection (ELND) is increasingly displaced by the Sentinel-lymph node biopsy. In this view we analyzed the efficacy of ELND in the treatment of malignant melanoma of the extremities and the trunc. Between 1979 and 1998 we performed a lymph node dissection in 834 patients (336 male, 498 female; average age 52 years). The analysis of the prospectively collected data was based on those 650 patients in whom an ELND was performed for UICC-stage I (T2) to stage III melanoma. The 5-year survival rate was 75% for all 650 patients. It was 87% for patients suffering from stage I-disease (T2-n = 65), 86% for those with stage II-disease (n = 354) and 47% in case of stage III-disease (n = 231) respectively. In 7 of the 73 patients undergoing ELND for a T2-tumor, in 56 of the 424 patients suffering from T3-tumor and in 38 of the 153 patients with a T4-tumor clinically obvious lymph node metastases had been detected by ELND. Discerning our results, we could demonstrate that a few of our patients profited from ELND, namely the patients in those clinically obvious metastases could be detected and survival could be achieved, i.e. 29 of all 650 electively dissected patients (2 of 7 T2N1-patients, 18 of 56 T3N1-patients and 9 of 38 T4N1-patients). We regard this benefit as an argument not to abandon the histological evaluation of the regional lymph nodes. However, because of the limited efficacy of elective lymphadenectomy, ELND should be displaced by the less invasive Sentinel-lymph node biopsy.

Adolescent↗
PubMed2001

Accumulation of fluconazole in sebum.

Concentrations of fluconazole in sebum and plasma were determined in 2 parallel groups, each consisting of 8 healthy subjects. Group 1 received a 150 mg fluconazole capsule once weekly over a period of 4 weeks, Group 2 was administered 2 capsules/week, corresponding to 300 mg fluconazole/week for 4 weeks. Sampling was performed immediately before and 5 hours after dosing, and at intervals up to 2 weeks after the last dose. Fluconazole concentrations were determined by a specific and highly sensitive gas chromatographic method. Both treatments were well tolerated. Maximum fluconazole concentrations (mean +/- SD) in plasma were 3.5 +/- 1.0 microg/ml (Group 1) and 5.5 +/- 1.0 microg/ml (Group 2); maximum sebum concentrations were 11.0 +/- 8.4 microg/g (Group 1) and 48.4 +/- 37.0 microg/g (Group 2). Significant accumulation of fluconazole in sebum relative to plasma was observed. Sebum/plasma ratios ranged from 1.6 to 6.5 (Group 1) and from 4.3 to 27.9 (Group 2), with median ratios of 2.4 and 9.1, respectively. The overall accumulation factor was 7. The findings may be of particular relevance for the treatment of dermal mycoses involving the sebaceous glands, especially those associated with hair, such as tinea capitis.

Adult↗
PubMed2000

Isolation and characterization of rheumatoid arthritis synovial fibroblasts from primary culture--primary culture cells markedly differ from fourth-passage cells.

To reduce culture artifacts by conventional repeated passaging and long-term culture in vitro, the isolation of synovial fibroblasts (SFB) was attempted from rheumatoid arthritis (RA) synovial membranes by trypsin/collagenase digest, short-term in vitro adherence (7 days), and negative isolation using magnetobead-coupled anti-CD14 monoclonal antibodies. This method yielded highly enriched SFB (85% prolyl-4-hydroxylase+/74% Thy-1/CD90+ cells; <2% contaminating macrophages; <1% leukocytes/endothelial cells) that, in comparison with conventional fourth-passage RA-SFB, showed a markedly different phenotype and significantly lower proliferation rates upon stimulation with platelet-derived growth factor and IL-1beta. This isolation method is simple and reliable, and may yield cells with features closer to the in vivo configuration of RA-SFB by avoiding extended in vitro culture.

Arthritis, Rheumatoid↗
PubMed2000

In vivo uptake of azithromycin in human coronary plaques.

Ten patients with symptomatic coronary artery disease received oral azithromycin for 3 days and underwent directional atherectomy on the third day. Azithromycin was found in all plaque samples with a median concentration of 284 ng/ml (95% confidence interval 163 to 517 ng/ml).

Anti-Bacterial Agents↗
PubMed2000

[Left ventricular diastolic function in normal pregnancy. A prospective study using M-mode echocardiography and Doppler echocardiography].

BACKGROUND AND OBJECTIVE: During pregnancy many substantial changes occur in the cardiovascular system. Aim of this study was to examine how physiological preload alterations influence left ventricular haemodynamic parameters. PATIENTS AND METHODS: During the 9th, 24th and 33rd weeks of pregnancy and 8 weeks after childbirth 36 patients underwent echocardiographic studies. 36 young not pregnant women (25 +/- 7 years) served as controls. The following Doppler echocardiographic parameters were measured: peak early diastolic flow velocity (VE, ms); acceleration (AT; ms) and deceleration time (DT; ms) of flow velocity in early diastole; peak late diastolic flow velocity (VA; m/s) and isovolumetric relaxation time (IVRT; ms). In all women the left ventricular muscle mass index (LVMMI), fractional shorting (FS; %) and the ratio between septum and posterior ventricular wall were calculated. RESULTS: During pregnancy all women showed an elevation of the left ventricular muscle mass index (LVMMI: from 66 +/- 6 to 100 +/- 9 g/m2; p < 0.01) and a decrease of fractional shortening (FS: from 38 +/- 4 to 31 +/- 3%). All patients developed a relevant diastolic dysfunction: reduced early diastolic flow velocity (VE: from 0.89 +/- 0.11 to 0.83 +/- 0.19 m/s; P < 0.01), reduced E/A ratio (1.7 +/- 0.4 to 1.2 +/- 0.4; P < 0.01), prolonged IVRT (72 +/- 12 to 114 +/- 12 ms; P < 0.01) and deceleration time (DT: to 189 +/- 17 to 227 +/- 18 ms; P < 0.01). Eight weeks after childbirth all parameters of left ventricular systolic and diastolic functions were normal. CONCLUSION: Preload alterations during normal pregnancy lead to reversible physiological left ventricular hypertrophy. Furthermore, we found a short-time reduction of systolic function just before childbirth and a significant alteration of the left ventricular diastolic filling pattern (abnormal relaxation pattern). While left ventricular systolic function was normal in all patients one week after childbirth, left ventricular hypertrophy and left ventricular diastolic dysfunction persisted for nearly two months.

Adult↗
PubMed2000

The efficacy of adjuvant cytostatic therapy after organ transplantation for malignancy: an experimental study with a combined transplantation/tumor model.

New data show that perioperative cytostatic therapy is beneficial in the case of liver transplantation for hepatic cancer. However, it has not been established clearly whether chemotherapy interferes with graft rejection. We therefore studied the interactions between tumor growth and graft rejection, especially with regard to chemotherapy, using a combined tumor/transplantation model. As a tumor model, we used the Novikoff hepatoma, a malignant hepatoma that was injected subcutaneously into the backs of rats. Heterotopic heart grafting served as the transplantation model. In a first step (a), we studied the effect of cytostatic therapy on tumor growth: tumor cells were injected, and in four groups epirubicin, cyclosporine, epirubicin + cyclosporine, and placebo were applied, in corresponding groups, transplantation was additionally performed. Tumor growth was measured and the resected tumors were examined by histology and immunohistology. In a second step (b), we studied the effect of chemotherapy on graft rejection: transplantation was performed and the above-mentioned drugs were applied; in corresponding groups, a solid tumor was additionally induced and resected immediately before transplantation. The results of these procedures were as follows: (a) Epirubicin decreased tumor growth and diminished the volume-increasing effect of cyclosporine significantly. After transplantation, tumor growth was similar. (b) Epirubicin prolonged graft survival significantly, and the combination with cyclosporine had an augmenting effect. In the corresponding groups, graft survival was similar. In conclusions. chemotherapy diminishes the tumor-increasing effect of cyclosporine and does not interfere negatively with graft survival. It might therefore be beneficial after transplantation for malignancy.

Animals↗
PubMed2000

[Sonographic changes after total hip joint replacement].

UNLABELLED: The value of ultrasonographic imaging after total hip arthroplasty (THA) has not been described in the literature so far. AIM: The typical postoperative sonographical findings are to be presented thus creating a basis for detecting pathological alterations. METHOD: 73 consecutive patients after THA were sonographically and clinically examined at the beginning and the end of the clinical rehabilitation phase. Laboratory tests detecting signs of inflammation and coagulation disorders were also performed. RESULTS: In the early postoperative phase collection of liquid and its delayed resorption are the most important findings. The haematoma of the joint is usually organised within three weeks after the operation. It could be visualised in all patients as a region of homogeneous, slightly echogenic appearance--not clearly distinguishable from the surrounding tissue and not compressible. Areas of low echogenicity were rarely seen. The forming of a neo-capsule could be detected from the ninth postoperative week onwards. Peri-articular ossification was not seen in this study. A loosening of prosthetic material did not occur. In the area of surgical approach irregularly shaped slightly echogenic and hardly compressible zones representing large haematomas could be found. The volume of these lesions could not be measured exactly due to their highly irregular shape. We did not observe large areas of seroma or liquid haematoma interfering with the rehabilitation process. CONCLUSION: Experienced examiners are capable of demonstrating the sonographic features representing signs of the healing process. Thus pathological developments can be detected and adequate therapeutic measures be taken. Future studies will have to show to which degree ultrasonography can become relevant in the diagnosis of endoprosthetic loosening.

Adult↗
PubMed2000

Sex differences in 'climacteric symptoms' with increasing age? A hypothesis-generating analysis of cross-sectional population surveys.

Are the established clinical symptoms of the female climacteric really specific for women? We were interested to compare the prevalence of these symptoms across age and sex. In the absence of longitudinal (cohort) studies, we tried to find cross-sectional, population-based studies with a broad age span to find a preliminary answer. We obtained six surveys that contained information for at least some of the symptoms. We re-analyzed these databases, which included over 8000 males and 8000 females, in a pooled fashion. Sixteen symptoms of predominantly somatic, psychological and urogenital origin were identified and the age-dependent increase of the relative frequencies was compared between genders. A general tendency for women to report more symptoms was confirmed; however, no significant differences were found between genders regarding the time trend of these symptoms. The analyses suggest that males experience a similar symptomatology in the same age span as women. One may thus be tempted to conclude that aging males experience similar phenomena to women during their menopausal transition. This should be confirmed in a specifically designed study.

Journal Article↗
PubMed2000

Expression of the multidrug-resistance 1 (MDR1) gene and prognosis in human pancreatic cancer.

Multidrug-resistance 1 (MDR1) encodes a 170 kDa transmembrane glycoprotein (P-glycoprotein), which acts as a drug-efflux pump. In the present study, we analyzed the expression of MDR1/P-glycoprotein in human pancreatic cancer and correlated the results with clinical parameters. Pancreatic cancer tissue samples were obtained from 67 patients (30 female, 37 male) who underwent surgery. Normal pancreatic tissues obtained from 15 previously healthy organ donors (4 female, 11 male) served as controls. MDR1 mRNA levels were analyzed by Northern blotting, and the exact site of MDR1 mRNA expression was determined by in situ hybridization and immunohistochemistry. Northern blot analysis indicated that in comparison with the normal pancreas, MDR1 mRNA levels were only increased 1.4-fold (p = 0.03) in the pancreatic cancer samples. However, there was a 2.9-fold (p < 0.01) increase in MDR1 mRNA levels when only the samples that exhibited increased expression (38%) were analyzed. In situ hybridization and immunohistochemical analysis showed that MDR1 was highly expressed in the cancer cells of these samples. Statistical analysis revealed that patients with high MDR1/P-glycoprotein expression had a shorter postoperative survival time compared with patients with weak to moderate expression of MDR1. On the basis of in situ hybridization, survival in the intense group was 11.6 (n = 12) versus 14.2 months (n = 42) in the mild to moderate group. On the basis of immunohistochemistry, survival in the intense group was 7.5 months (n = 10) versus 14.1 months (n = 40) in the mild to moderate group. Surprisingly, survival of patients with high expression of MDR1/P-glycoprotein was not significantly different from that of patients without detectable MDR1/P-glycoprotein expression. These findings suggest that both strong expression of MDR1/P-glycoprotein and lack of expression seem to influence tumor growth via known and yet unknown mechanisms.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2000

On the photochromism of spiro

The recently synthesized spiro[cyclohexadiene-dihydroacridines] consisting of perpendicularly arranged aroylcyclohexadiene and N-methyl-dihydroacridine moieties were found to have photochromic properties. The reversible photoisomerization from the spiro compound toward a colored merocyanine caused by C-C bond cleavage in the cyclohexadiene was studied by stationary and time-resolved measurements of their optical spectra. The course of the absorption under UV and visible irradiation, respectively, and HPLC analysis of the photoproducts result in the determination of excitation energy-dependent quantum yields for the merocyanine formation and, in reverse, the ring closure, as well as degradation. Whereas the thermal back reaction completely recovers the spiro compound (k approximately 6.8 x 10(-4) s-1, T = 22 degrees C), degradation of the merocyanine under irradiation at 480 nm has a probability of about 6%. Picosecond-resolved measurements of the fluorescence and the transient absorption show that photoisomerization occurs via the first excited singlet state within 100 ps depending on the activation barrier.

Journal Article↗
PubMed2000

The effects of Valette on skin and hair: a post-marketing surveillance study.

The effects of Valette--an oral contraceptive containing ethinyloestradiol 0.03 mg and the antiandrogenic progestogen dienogest 2.0 mg--on the skin and hair were surveyed over 63,474 cycles in 10,718 women in routine gynaecological practice. Improvements were greatest in women with severe or moderate androgen-related symptoms. After six cycles, < 1% of women had severely greasy hair and 6% had moderate greasiness, compared with 11% and 27% at baseline; fewer hair washes were needed per week. The incidence of severe and moderately greasy skin disorders fell from 16% to < 1%, and from 39% to 7.5%, respectively. Self-assessments indicated less greasy hair and improved greasy skin disorders in 70% and 81% of women, respectively. The overall effect of Valette on the skin and hair was rated very good or good by 87.5% of women. These results confirm previous observations of a beneficial effect of Valette on androgen-related skin and hair conditions.

Adolescent↗