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Biomedical subjects

U Otto

Publications and source records attributed to U Otto.

At least 19 recordsLinked to original sources

Alternative shift models and the quality of patient care. An empirical study in surgical intensive care units.

UNLABELLED: On 1 January 1996, the German Arbeitszeitgesetz (working-time regulation) came into effect for hospital physicians. It states that working hours must not exceed 8 h per day, even for physician in hospitals. As a consequence, the prevalent two-shift model is legally inadmissible. The intention of this law is to protect the physician and to create better conditions for the patients. However, a systematic evaluation of the postulated benefits is still lacking. AIM: The aim of our study was to analyze the influence of the length of daily working hours on the quality of patient care by measuring the outcome of patients in intensive care units (ICUs), comparing the two-shift model (2-SM)--two 12-h shifts--with the three-shift model (3-SM)--three 8-h shifts. MATERIALS AND METHODS: In a prospective multicenter study, we compared the outcome of patients in six ICUs (organized by surgeons) with different models of working hours. The health status of each patient and the course on ICU [described by hospital mortality, number of complications, readmission to the ICU, reinterventions, duration of the stay in an ICU and hospital, the course of the Acute Physiology and Chronic Health Evaluation (APACHE) II score] were uni- and multivariately analyzed. In addition, the technical and personnel resources of the ICUs and the hospitals were documented. RESULTS: Three hundred and forty seven patients (103 2-SM, 244 3-SM) were included. The epidemiological and the health status on admission to the ICU were comparable. Patients in the 3-SM stayed 1.6 days longer on ICU and 2.3 days longer in the hospital than the 2-SM patients. The frequency of complications, reinterventions, and readmissions to ICU was higher in the 3-SM. The median of the APACHE-II score decreased more for 2-SM than for 3-SM patients. This means a significantly quicker recovery of the patients in 2-SM (P < 0.05). The multivariate analysis with individual outcome measures as dependent variables revealed a significant positive effect of the 2-SM on the physicians' assessment of postoperative course, on the relative frequency of therapeutic procedures, and to a lesser extent on the duration of stay in the ICU.

APACHE↗

[Percutaneous stereotactic biopsy of non-palpable breast lesions using the Advanced Breast Biopsy Instrumentation (ABBI) system: critical evaluation of indication strategies].

PURPOSE: To compare the indications for biopsy with and without the use of the Breast Imaging Reporting and Data System. MATERIAL AND METHODS: Biopsies using the ABBI were performed in 62 patients with 64 non-palpable evident mammographic lesions. The initial decision for biopsy was made by non-radiologists due to suspicious microcalcifications (n = 53) and masses (n = 11). The indication was retrospectively reassessed by adopting the BI-RADS classification by three radiologists in consensus. The positive predictive value (PPV) of both indication strategies was assessed and compared. RESULTS: Biopsies adopting ABBI were performed without major side-effects and were diagnostic. Carcinoma was present in 14 lesions: nine specimens were diagnosed as DCIS and five as invasive carcinomas. For the 50 benign lesions histology revealed mastopathies (26/50) and fibroadenomas (8/50) as the most frequent diagnosis. The positive predictive value (PPV) for the initial indication was 22%, whereas PPV for BI-RADS based indications (categories 4 and 5) was 31%. CONCLUSION: ABBI enables stereotactically-guided procedures that result in representative and diagnostic biopsies. Standardized criteria like BI-RADS improve the PPV and should be a mandatory part of mammographic evaluation. Radiologists should remain involved in the decision making.

Adult↗

More cerebellar granule cells following prenatal low-dose X-irradiation.

It was the aim of this study to estimating and comparing the total number of granule and Purkinje cells in the cerebellum of 180-day-old mice following a prenatal low-dose X-irradiation (50 cGy) at day 13 of gestation. Using the optical fractionator we found an expected, significant decrease of the total number of Purkinje cells (-21.1%; P=0.041) and a surprising, significant increase of the total number of granule cells (+23.1%; P=0.026) if comparing prenatally irradiated with sham-irradiated mice. The possible molecular basis of these seemingly paradoxical results is discussed.

Animals↗

An evaluation of telemedicine in surgery: telediagnosis compared with direct diagnosis.

HYPOTHESIS: Telemedicine for real-time transmission of clinical documents and interactive remote telediagnosis allows accurate clinical application in surgery. DESIGN: Prospective cohort study in which 2 hospitals, 120 miles apart, were connected via integrated services digital network (ISDN) teleconferencing units, and each evaluated clinical cases in real time. SETTING: A tertiary care university hospital and primary care county hospital. PARTICIPANTS: Between May 1, 1998, and June 30, 1998, 112 patients undergoing digestive or endocrine surgery were evaluated by teletransmission (study group) and direct vision (control group). Diagnosis had to be known by the viewer, and either conventional magnetic resonance imaging or computed tomographic scans were available. MAIN OUTCOME MEASURES: Picture quality, organ structure, and pathologic finding viewed on telemedicine documents were evaluated by radiologists and surgeons blind to diagnosis. Accuracy of remote 128-kilobit (kb)/s transmission-rate diagnoses and results were compared with those obtained directly. RESULTS: Picture quality was "good" or "excellent" in 92.9% of transmitted documents and 95.5% of live images (P>.4). The target organ was always recognized, structure and pathologic finding were analyzable in 98.2% of transmitted documents and 99.1% of live documents, and fine structures were assessable in 89.3% of transmitted pictures and 95.5% of live pictures (P>.05). Diagnosis was made in 84.8% of transmitted cases and 93.8% of live cases (P = .02). CONCLUSIONS: Low bandwidth (128 kb/s) telemedicine application in surgery is reliable in evaluating remote cases. Loss of image quality through teletransmission occurred in 2.7% of cases, and diagnosis was not possible in 15.2% of transmitted vs 6.2% of live cases, suggesting factors other than technical quality (choice of radiological studies, additional clinical information required, etc). This underscores the importance of real-time interactive discussion during surgical teleconferences.

Cohort Studies↗

Growth of human prostate carcinomas with and without hormone alpha- dehydrotestosterone in nude mice.

OBJECTIVES: The dependence of human prostate carcinoma growth on hormone was studied in xenotransplants in nude mice. The objective was to determine differences in cell kinetic parameters and volume growth of tumors growing with alpha-dehydrotestosterone (alphaDHT) and without alphaDHT. These differences could be used as arguments pro and contra the adaptation versus the clonal selection hypothesis. METHODS: Human prostate carcinomas were xenotransplanted into nude mice. Growth of tumors was observed in castrated male mice without and with implanted osmotic pumps secreting alphaDHT. In a further series of experiments the alphaDHT tubes were removed when the tumors had reached a volume of 0.3 cm3. Tumor volume was measured to determine tumor doubling time with and without alphaDHT. Detailed cell kinetics were analyzed using the bromodeoxyuridine (BrdUrd) method with flow cytometry. Applying the relative movement (RM) and a simulation analysis to parallel single and multiple BrdUrd labelling experimental data we determined transit times through the phases of cell cycle, potential doubling time Tpot, growth fraction (GF) and cell loss. RESULTS: Five human prostate carcinomas were xenotransplanted into nude mice. Tumor take was only achieved when androgen hormone was present. However, when alphaDHT was removed when the tumors had grown to a volume of 0.3 cm3, they continued to grow at nearly the same Td as those tumors with continued alphaDHT application. The BrdUrd experiments, on the other hand, showed considerable increase of Tc and Tpot upon withdrawal of alphaDHT in 4 out of 5 tumors. The GF and labelling index (LI) were maintained at about the same level as alphaDHT consuming tumors. CONCLUSION: While small transplanted tumor pieces do not grow without alphaDHT, larger tumors grow with the same Td after removal of alphaDHT. The slower proliferation shown by the increased Tc and Tpot is balanced by less cell loss. Since GF and LI were maintained at about the same level, we conclude that in our tumors the majority of cells adapted to hormone independence. There was no evidence for the selection model since the tumors continued to grow at about the same speed after hormone depletion. All cell kinetic parameters showed a considerable inter- and intratumoral heterogeneity. A clinical implication may be that hormone ablation therapy should always be supplemented by some other therapy.

Animals↗

Heterogeneous cell kinetics in tumors analyzed with a simulation model for bromodeoxyuridine single and multiple labeling.

Bromodeoxyuridine (BrdUrd) labeling of DNA and flow cytometry measurement of bivariate BrdUrd-DNA content distributions yield proportions of cells in the cycle phases. After application of BrdUrd, with time, these proportions change according to the cell kinetic parameters of the investigated cell line or tumor. In a previous study of S-phase transit time using the relative movement method, we obtained better fits with S-duration distributions rather than constant values (Baisch and Otto: Cell Prolif 26:439-448, 1993). Now, we have developed a simulation model using asymmetric phase duration distributions in all phases of the cell cycle to fit the experimental data after single or multiple BrdUrd labeling. The model includes transit of cells from proliferating to quiescent compartments in all phases. The results yield the phase duration distributions, mean and median percentages of quiescent cells in all phases, growth fraction, and potential doubling time. The model was used to fit data of five renal cell carcinomas xenotransplanted into nude mice that were obtained after single and multiple labeling up to 93 hours. The estimated phase duration distributions varied from narrow to extremely asymmetric. In particular, TG2M duration and asymmetry were nearly as large as those of G1 phase in some tumors. The contribution of inter- and intratumoral heterogeneity cannot be separated by the simulation model, but evidence of intratumoral heterogeneity is provided by DNA content distributions at extended time spans after BrdUrd labeling.

Animals↗

Intratumoral heterogeneity of S phase transition in solid tumours determined by bromodeoxyuridine labelling and flow cytometry.

Cell kinetics of human renal cell carcinomas xenotransplanted into nu/nu mice were analysed using the bromodeoxyuridine (BrdUrd) labelling method. Tumours were removed 0.5-14 h after injection of the BrdUrd solution. The tumour cells were stained with fluorescein isothiocyanate conjugated anti-BrdUrd antibodies and propidium iodide (DNA content). From the flow cytometry data the relative movement was calculated. Relative movement data of variable intervals after BrdUrd labelling were subjected to a fit procedure using log-normal distributions for S phase transition (T(s)). The log-normal distributions were modified by inflation factors in order to get extremely asymmetric distributions. The best fits to the experimental data were obtained using wide asymmetric T(s) distributions, indicating that progression through S phase in solid human tumours is considerably heterogeneous. This implies that the potential doubling time (T(pot)) is longer than calculated from a single measured relative movement value obtained a few hours after BrdUrd labelling.

Animals↗

[Androgen regulation of secreted growth factors in prostate carcinoma cell and tumor lines].

Previous studies have shown that part of steroid hormone action on hormone dependent carcinoma cells is mediated through secreted autocrine and paracrine growth factors. Coculture experiments using the androgen receptor positive human prostate carcinoma cell line LNCaP as feeder cells and the androgen receptor negative prostate cell line DU 145 as indicator cells, such as experiments with conditioned medium suggest that androgens might regulate proliferation of prostate carcinoma through a similar mechanism. LNCaP and DU 145 cells express high affinity EGF-receptors and show an increased growth rate under treatment with EGF, TGF alpha and FGF. The growth stimulating potential of LNCaP-conditioned medium can be enhanced by androgens. The polyanionic compounds suramin and dextran sulfates which have been shown to inactivate a variety of growth factors e.g. EGF/TGF alpha inhibit growth of LNCaP cells and DU 145 cells in a dose dependent and reversible fashion. Growth stimulation of LNCaP cells by EGF/TGF alpha can be completely reversed by simultaneous addition of polyanions but they inhibit androgen stimulation only partially. These data suggest the existence of at least two different mechanisms of growth regulation by androgens which can be distinguished by their different sensitivity of prostatic carcinoma cells to growth factor inhibitory agents. In order to investigate the therapeutic potential of these substances in complex, heterogeneous cell systems of solid tumors we treated 8 representative human prostate cancer lines in the nude mouse model. Systemic applications of polyanions revealed significant growth inhibition in hormone dependent as well as hormone independent xenografts. In androgen responsive lines growth inhibition was intensified by additional androgen withdrawal.(ABSTRACT TRUNCATED AT 250 WORDS)

Androgens↗

Recombinant interferon alfa-2a with or without vinblastine in metastatic renal cell carcinoma: results of a European multi-center phase III study.

A total of 178 patients with metastatic renal cell cancer were randomized to receive interferon alfa-2a (rIFN alfa-2a) or interferon alfa-2a+vinblastine (VLB). IFN alfa-2a was injected intramuscularly at a dose of 18 MIU 3 times a week and VLB was given intravenously at a dose of 0.1 mg/kg once every 3 weeks. The response rate was 11% for patients on monotherapy and 24% for those on combination treatment. The 5-year survival for 145 eligible patients was 9%, independently from the treatment arm. The performance status was significantly related to long-term prognosis, and 13% of the patients with performance status 0 were alive at 5 years, as compared to 6% and 0% for patients with a WHO grade of 1 and 2, respectively. The most frequent adverse events in both treatment arms were flu-like symptoms (95%), fatigue (70%) and gastrointestinal disturbances (68%). Leukopenia was observed more frequently with combination treatment (53%) than with IFN alfa-2a alone (30%). In conclusion, rIFN alfa-2a monotherapy at this dose and schedule has modest antitumor activity in metastatic renal cell cancer. The combination of rIFN alfa-2a+VLB results in a doubling of the response rate, but this does not translate into prolonged survival. Toxicity (except leukopenia) and tolerance were similar in both treatment arms.

Adult↗

Transplantation of human benign hyperplastic prostate tissue into nude mice: first results of systemic therapy.

Xenografts of human benign hyperplastic prostate tissue (BPH) have been established as a model for the investigation of the etiology of BPH. In this paper it is our aim to answer the question of whether this model is useful for the established therapy of the disease. Additionally we try to evaluate the value of a commonly used plant extract for the therapy of BPH. Is there any influence of the extract from Sabal serrulatum on the BPH tissue in our model? Human BPH tissue from 2 patients was transplanted into athymic nude mice and treated with three different regimens. Animals of group I did not receive any treatment and served as control, in groups II and III the tissue was stimulated by application of silicone tubes containing crystalline 5 alpha-dihydrotestosterone and estradiol. Animals of group II additionally were treated orally with the lipophilic extract of S. serrulatum (contained in Prostagutt N), which is commonly used for the treatment of BPH clinically. Significant inhibition of tissue growth was observed in group III when compared to group II. In group I (control) atrophy of the graft was observed as expected. However, histologically no differences were visible between groups II and III. Our experiment shows a significant growth-inhibiting effect of the plant extract for human BPH tissue in our model (p less than 0.05). We conclude that the nude mouse model can be useful for the evaluation of systemic therapy modalities of human BPH and that the plant extract may have a certain value for clinical treatment, which is not only due to subjective criteria.

Animals↗

Swedish UN soldiers in Cyprus, UNFICYP: their psychological and social situation.

Two Swedish rifle batallions serving as UN soldiers in Cyprus (UNFICYP) have been investigated with respect to their demographic background and motives for application for UN service. The comparison of symptoms of stress in general, of posttraumatic stress disorder specifically, and some other variables of reaction with various studies of Swedish UN soldiers in different settings has given the following results. Very few interviewees experienced 'personal nervous breakdown' (0.5%). The soldiers reported in general very few psychological or psychosomatic complaints in the short time perspective. There seemed, however, to be two groups of persons at risk, namely those who were repatriated and those with a high consumption of alcohol.

Adult↗

[Obstructive uropathy after kidney transplantation. Experiences with endourologic incision of ureteral stenoses].

Between 1985 und March 1991 we have managed 8 upper urinary tract obstructions in kidney transplants using an endourological approach. After a graft rejection was excluded an obstruction was initially diagnosed by nephrosonography and further confirmed by IVP or antegrade pyelography. To investigate the urodynamic relevance of the stenosis, all patients underwent preoperative diuretic isotope renography. In all cases a percutaneous pyelostomy was done to preserve renal function. 7 of these 8 patients demonstrated a stenosis of the ureter, while in one case, the obstruction was caused by a coagulum in the renal pelvis. Incision of the stricture then was performed with a flexible knife antegrade or retrograde and stented for 4-6 weeks. In 6 out of 7 cases with a proven stenosis of the ureter, the cold knife incision lead to a successful outcome, while in one patient, the kidney had to be removed due to uncontrolled bleeding 12 days after successful percutaneous incision. Our results indicate, that the cold-knife-technique for the management of upper urinary tract obstructions in kidney transplants is a promising, fast and in most of the cases effective method. Due to its minimalinvasive character and excellent results, this approach is able to replace open reintervention in most cases.

Adolescent↗

[Vasovasostomy after vasectomy. The surgical results 1986-1989].

The frequency of vasovasostomy has increased dramatically in recent years. A significant percentage of men who have previously undergone vasectomy are now seeking restoration of their fertility. The most common reason for requesting a reversal is remarriage. There were 90 bilateral vasovasostomies performed in 90 patients between 1986 and 1989. The procedure was done according to the technique described by Howards, in a single layer with 7 x 0 prolene and under fourfold magnification. The success rate was 87% for presence of spermatozoa in the ejaculate, 48% for pregnancy. The fertility rate decreases slowly with increasing interval between vasectomy and reanastomosis. These results are statistically significant. In cases of good anatomical and andrological conditions, the chance of restoration of fertility is good. The experience of the urologist is often more important than the details of the technique.

Adult↗

The cold-knife technique for endourological management of stenoses in the upper urinary tract.

Between 1985 and October 1989 we managed 13 patients with primary and 43 with secondary obstruction of the upper urinary tract with the endourological cold-knife technique. We treated 26 patients with stenosis of the ureteropelvic junction, 9 with infundibular stenosis, 12 with ureteral obstruction after inflammation or radiation therapy, 7 with stricture of the ureter in kidney transplants and 2 with stenosis of the ureter after ureterosigmoidostomy. Endourological management was successful in 42 of 56 cases with a decrease or total elimination of obstruction. Stenosis recurred in 9 patients. Our results indicate that the cold-knife technique should be attempted as the initial approach in all cases of primary or secondary obstruction of the upper urinary tract.

Adolescent↗

[Pheochromocytoma of the urinary bladder. Diagnosis and therapy based on a case report].

Micturition difficulties associated with unstable hypertension, tachycardia and profuse sweating could be a sign of pheochromocytoma of the urinary bladder. Of all pheochromocytomas, 10-36% are located extradrenally, in which case they are also referred to as paragangliomas, and 1-3% are found in the urinary bladder. The case history of a 44-year-old female patient with typical symptoms is described. Diagnosis required not only CT, NMR, excretory urography and MIBG scintigraphy, but also hormonal analyses. Histology reveals malignancy in up to 20%; it is thought that focal invasions of tumor into vessels and destruction of connective tissue might be pathognomonic. A precise history and careful diagnosis are necessary before a pheochromocytoma of the bladder can be disclosed and treated.

Adult↗

Antiproliferative and cytotoxic effects of single and combined treatment with tumor necrosis factor alpha and/or alpha interferon on a human renal cell carcinoma xenotransplanted into nu/nu mice: cell kinetic studies.

A human renal cell carcinoma serially transplanted into nude mice was treated with recombinant human tumor necrosis factor alpha (TNF-alpha), recombinant human alpha interferon (IFN-alpha), and a combination of both. All treatments resulted in a significantly reduced tumor growth. The greatest effect was obtained with the combination of TNF-alpha and IFN-alpha. This latter treatment completely eradicated tumors which were smaller than 50 mm3 at the beginning of treatment. Cell kinetic analysis using the bromodeoxyuridine technique and flow cytometry revealed a prolongation of the transition time through S-phase from 7.9 h in the case of control tumors to 10.5 h for tumors treated with IFN-alpha and TNF-alpha. Single treatment with either TNF-alpha or IFN-alpha had only minor effects. The bromodeoxyuridine labeling index was unaffected by IFN-alpha (16.6%; control, 15.2%) but was reduced to 12.1 and 11.7% when tumors were treated with TNF-alpha and IFN-alpha plus TNF-alpha, respectively. The calculated potential doubling times were 2.3 and 2.8 days, respectively, for tumors treated with TNF-alpha or IFN-alpha plus TNF-alpha. When treated with IFN-alpha, the potential doubling time (1.7 days) was similar to that of the control (1.6 days), indicating that the main effect of TNF-alpha was antiproliferative. Conversely, the calculated cell loss factors increased after IFN-alpha and combined treatment but not after TNF-alpha treatment. Combined treatment augmented cytotoxicity, but the cell kinetic characteristics of surviving cells remained similar to those of tumors treated with TNF-alpha alone. Histological analysis showed a distinctly reduced mitotic activity but no coagulative necroses after treatment with TNF-alpha. IFN-alpha and, in particular, IFN-alpha plus TNF-alpha induced cytoplasmic vacuolization, nuclear pyknosis, and cell death, which resulted in tumor regression. These data suggest that, in this particular tumor model, TNF-alpha produces mainly antiproliferative effects, whereas IFN-alpha acts via cytotoxic mechanisms.

Animals↗

Comparison of different schedules of cytostatic intravesical instillations in patients with superficial bladder carcinoma: final evaluation of a prospective multicenter study with 419 patients.

In a prospective multicenter study we compared the value of various protocols of mitomycin C and doxorubicin instillation for the prevention of recurrent tumors in patients whose superficial bladder tumors (stages TA and T1) had been removed by transurethral resection. The 3-year and short-term instillation protocols were compared to each other and to a combination of 2 protocols. Evaluation after a mean followup of 28 months confirmed the value of cytostatic bladder instillation in preventing recurrence and progression of tumor in patients with superficial bladder carcinoma. There was no significant difference between the results of long-term and short-term prophylaxis; their combination achieved the best results. Doxorubicin and mitomycin yielded similar results; mitomycin was better tolerated.

Administration, Intravesical↗