Cortical Flow-Driven Shapes of Nonadherent Cells.

Nonadherent polarized cells have been observed to have a pearlike, elongated shape. Using a minimal model that describes the cell cortex as a thin layer of contractile active gel, we show that the anisotropy of active stresses, controlled by cortical viscosity and filament ordering, can account for this morphology. The predicted shapes can be determined from the flow pattern only; they prove to be independent of the mechanism at the origin of the cortical flow, and are only weakly sensitive to the cytoplasmic rheology. In the case of actin flows resulting from a contractile instability, we propose a phase diagram of three-dimensional cell shapes that encompasses nonpolarized spherical, elongated, as well as oblate shapes, all of which have been observed in experiment.

A single-molecule approach to explore binding, uptake and transport of cancer cell targeting nanotubes.

In the past decade carbon nanotubes (CNTs) have been widely studied as a potential drug-delivery system, especially with functionality for cellular targeting. Yet, little is known about the actual process of docking to cell receptors and transport dynamics after internalization. Here we performed single-particle studies of folic acid (FA) mediated CNT binding to human carcinoma cells and their transport inside the cytosol. In particular, we employed molecular recognition force spectroscopy, an atomic force microscopy based method, to visualize and quantify docking of FA functionalized CNTs to FA binding receptors in terms of binding probability and binding force. We then traced individual fluorescently labeled, FA functionalized CNTs after specific uptake, and created a dynamic 'roadmap' that clearly showed trajectories of directed diffusion and areas of nanotube confinement in the cytosol. Our results demonstrate the potential of a single-molecule approach for investigation of drug-delivery vehicles and their targeting capacity.

PIK3R1 mutations in SHORT syndrome.

SHORT syndrome (OMIM 269880) is a rare autosomal-dominant disorder characterized by short stature, hyperextensibility of joints, hernias, ocular depression, ophthalmic anomalies (Rieger anomaly, posterior embryotoxon, glaucoma), teething delay, partial lipodystrophy, insulin resistance and facial dysmorphic signs. Heterozygous mutations in PIK3R1 were recently identified in 14 families with SHORT syndrome. Eight of these families had a recurrent missense mutation (c.1945C>T; p.Arg649Trp). We report on two unrelated patients with typical clinical features of SHORT syndrome and additional problems such as pulmonary stenosis and ectopic kidney. Analysis of PIK3R1 revealed the mutation c.1945C>T; p.Arg649Trp de novo in both patients. These two patients not only provide additional evidence that PIK3R1 mutations cause SHORT syndrome, but also broaden the clinical spectrum of this syndrome and further confirm that the amino acid exchange c.1945C>T; p.Arg649Trp is a hotspot mutation in this gene.

Evaluation of head and neck cancer with (18)F-FDG PET: a comparison with conventional methods.

The aim of this study was to evaluate the usefulness of (18)F-FDG PET in the diagnosis and staging of primary and recurrent malignant head and neck tumours in comparison with conventional imaging methods [including ultrasonography, radiography, computed tomography (CT) and magnetic resonance imaging (MRI)], physical examination, panendoscopy and biopsies in clinical routine. A total of 54 patients (13 female, 41 male, age 61.3±12 years) were investigated retrospectively. Three groups were formed. In group I, (18)F-FDG PET was performed in 15 patients to detect unknown primary cancers. In group II, 24 studies were obtained for preoperative staging of proven head and neck cancer. In group III, (18)F-FDG PET was used in 15 patients to monitor tumour recurrence after radiotherapy and/or chemotherapy. In all patients, imaging was obtained at 70 min after the intravenous administration of 180 MBq (18)F-FDG. In 11 of the 15 patients in group I, the primary cancer could be found with (18)F-FDG, yielding a detection rate of 73.3%. In 4 of the 15 patients, CT findings were also suggestive of the primary cancer but were nonetheless equivocal. In these patients, (18)F-FDG showed increased (18)F-FDG uptake by the primary tumour, which was confirmed by histology. One patient had recurrence of breast carcinoma that could not be detected with (18)F-FDG PET, but was detected by CT. In three cases, the primary cancer could not be found with any imaging method. Among the 24 patients in group II investigated for staging purposes, (18)F-FDG PET detected a total of 13 local and three distant lymph node metastases, whereas the conventional imaging methods detected only nine local and one distant lymph node metastases. The results of (18)F-FDG PET led to an upstaging in 5/24 (20.8%) patients. The conventional imaging methods were false positive in 5/24 (20.8%). There was one false positive result using (18)F-FDG PET. Among the 15 patients of group III with suspected recurrence after radiotherapy and/or chemotherapy, (18)F-FDG was true positive in 7/15 (46.6%) and true negative in 4/15 (26.6%). The conventional imaging methods were true positive in 5/15 (33.3%) and true negative in 4/15 (26.6%). One false negative (6.6%) and three false positive findings (20%) on (18)F-FDG PET were due to inflamed tissue. The conventional imaging methods were false positive in three (20%) and false negative in three cases (20%). It is concluded that in comparison to conventional diagnostic methods, (18)F-FDG PET provides additional and clinically relevant information in the detection of primary and metastatic carcinomas as well as in the early detection of recurrent or persistent head and neck cancer after radiotherapy and/or chemotherapy. (18)F-FDG PET should therefore be performed early in clinical routine, usually before CT or MRI.

[Pre-emptive analgesia with ropivacaine in adult tonsillectomy]. / Präemptive Analgesie mit Ropivacain bei Tonsillektomien im Erwachsenenalter.

AIM OF INVESTIGATION: We examined whether a pre-emptive analgesic effect could be achieved with ropivacaine, which has less cardiovascular and central nervous system toxicity than bupivacaine, in adults undergoing tonsillectomy. METHODS: The study was carried out in 80 patients in a randomised, double-blind fashion. The patients were randomly assigned to one of four groups. In group I, 3 ml ropivacaine 7.5 mg/ml were injected pre-operatively 5 minutes before the start of OR into each tonsil bed. In group II, 3 ml ropivacaine 7.5 mg/ml were injected post-operatively into each tonsil bed. In group III, 3 ml NaCl were injected pre-operatively 5 minutes before the start of OR into each tonsil bed. In group IV, 3 ml NaCl were injected post-operatively into each tonsil bed. The analgesic effectiveness was measured post-operatively by the use of a visual analogue scale, a numeric rating scale (at rest and during activity) and by measuring the total analgesic consumption (mefenamic acid) in the first 192 hours. In addition the time of first analgesic request was noted. Vital parameters and side-effects were documented. RESULTS: There was no significant difference between the groups in the time of first analgesic request. Likewise, there was no significant difference in the post-operative cumulative analgesic consumption between the four groups. The post-operative administration of ropivacaine resulted in significantly lower pain scores at certain time points compared with the other groups as measured both with the visual analogue scale and the numeric rating scale (at rest). It must be emphasized, that the pain scores both at rest and with exertion remain high and that the net analgesic consumption (per day) remains constant for the first 8 post-operative days. CONCLUSIONS: We could demonstrate no significant pre-emptive analgesic effect with ropivacaine in adults undergoing tonsillectomy in our study. One can, however, recommend the administration of ropivacaine post-operatively after tonsillectomy, since a reduction of pain scores can thereby be achieved. For post-operative analgesia we recommend the combination of a non-opioid analgesic with a weak opioid.

Hyaluronidase as additive to induction chemotherapy in advanced squamous cell carcinoma of the head and neck.

Forty-eight patients with advanced head and neck tumours were treated with irradiation and concomitant chemotherapy with cisplatin, vindesine and hyaluronidase. The disease-free survival rate at 5 years was 47%. The toxic effects were mucositis (48 patients), nausea (25 patients, vomiting in six patients), bone marrow depression (15 patients) and peripheral neuropathy (14 patients). The results warrant a randomized trial.

Combined application of cisplatin, vindesine, hyaluronidase and radiation for treatment of advanced squamous cell carcinoma of the head and neck.

In a prospective pilot study, 32 patients with advanced inoperable squamous cell carcinoma of the head and neck were treated with polychemotherapy and hyaluronidase combined with radiation therapy. Polychemotherapy consisted of 5 mg vindesine on day 1 and 80 mg/m2 cisplatin on day 2. The patients were given 200,000 IU hyaluronidase intravenously 20 minutes prior to vindesine and cisplatin. Radiation in fractions of 2 Gy per day was administered on the following days (days 3-5, 8-12, 15-18), that is, 12 times. This regimen was repeated twice starting with day 22 and 43. Side effects were mainly of local character: moderate to severe mucositis in 10 patients and mild mucositis in 22 patients. No severe systemic toxicity was observed. Complete remission was achieved in 27 of 32 patients. At present, 16 patients are alive and without relapse. The average time of follow-up is 47 months (range: 26-75 months). These preliminary results suggest that combined therapy with vindesine, cisplatin, hyaluronidase, and radiation are well tolerated by most patients and highly effective against advanced squamous cell cancer of the head and the neck.

The prognostic value of DNA ploidy and S-phase estimate in primary breast cancer: a prospective study.

In this prospective study, the independent prognostic value of DNA ploidy in combination with the major clinico-pathological characteristics (histological grade, nodal status, tumor size, estrogen and progesterone receptor status, number of tumors, multicentricity, lympho-vascular infiltration) was evaluated in a series of 399 breast-cancer patients. The mean follow-up time was 4.5 years. The DNA content was measured using image cytometry on fresh tumor samples. The overall survival of tetraploid and slowly proliferating diploid cases was significantly different compared with that of aneuploid and rapidly proliferating diploid cases (p = 0.0002). Thus, DNA ploidy combined with S-phase estimate (DNA histogram type) appeared to be good prognostic factors. In a multivariate survival analysis, DNA histogram type was not an independent prognostic factor unless the histological grade was excluded. This effect of DNA histogram type on survival was also observed among patients with grade-I or -II tumors and patients with small tumors. In conclusion, DNA histogram type was a valuable prognostic factor in univariate analysis, and provided independent complementary information for patients considered at low or intermediate risk by classical pathological findings.

Epidermal growth factor, transforming growth factor-alpha, and epidermal growth factor receptor content in normal and carcinomatous gastric and colonic tissue.

Epidermal growth factor (EGF) and transforming growth factor-alpha (TGF-alpha) are polypeptides which bind to the EGF receptor (EGFr) and may play a role in cell growth and carcinogenesis. Our study investigated the content of EGF, TGF-alpha, and EGFr in tumors of the stomach and the colon in comparison with the surrounding mucosa. EGF was detected in half of the stomach specimens with concentrations between 1 and 9 ng/g weight irrespective of histology. In the colon no EGF was found in the tumor or normal mucosa. In the stomach normal mucosa contained higher TGF-alpha concentrations (mean 22.4 ng/g) than the tumors (mean 11.8 ng/g), but the difference was not statistically significant because of a wide variation in mucosal values. By contrast, the colon mucosa displayed significantly higher TGF-alpha concentrations than the tumor tissues (33 ng/g versus 12 ng/g; P < 0.01). EGFr content in the gastric mucosa was lower compared to gastric carcinoma (48 fmol/g versus 75 fmol/g) yet not significantly different. In contrast, colorectal tumor specimens disclosed significantly higher concentrations than the mucosal tissues (mean of 155 fmol/g versus 80 fmol/g; P < 0.01). In conclusion, TGF-alpha should not be considered a tumorigenic but a physiological growth factor in the stomach and colon. An elevated EGFr content in colorectal tumors in comparison with the normal mucosa could lead to a growth advantage by an autostimulating mechanism.

Videotape dietary assessment: validity, reliability, and comparison of results with 24-hour dietary recalls from elderly women in a retirement home.

The validity and reliability of a videotape method for quantifying food intake were tested, and results of the method were compared with results obtained from 24-hour dietary recalls. Participants were 37 elderly Catholic nuns (aged 81.8 +/- 4.1 years) who were ambulatory and living in a retirement home. The videotape method of dietary assessment consisted of videotaping food trays of each participant for three meals during 1 day and the subsequent identification of food types and amounts from the videotapes. Estimates of food amounts obtained were used in the calculation of energy and nutrient intake. Correlation coefficients between values for energy and 14 nutrients obtained by direct measurement of food and estimates from the videotape method were high (r = 0.86 to 1.0). Compared with measured food amounts, the videotape method underestimated food quantities by an average of 6%. The reliability test indicated that mean nutrient values obtained from the videotape method by two research assistants differed by an average of 3.7% and were highly correlated (r = 0.84 to 0.98). Comparison of the videotape method with 24-hour dietary recalls revealed differences between mean values that were greater than 10% for energy and 6 of the 14 nutrients and correlations that ranged from 0.09 to 0.82. These results suggest that use of 24-hour dietary recalls among the elderly may result in a high percentage of error.

[Radioactive cesium 137 and cesium 134 in follicle and seminal fluid]. / Radioaktives Cäsium 137 und Cäsium 134 in der Follikel- und Samenflüssigkeit.

Radioactive caesium nuclids were measured in follicular fluid and seminal plasma after the nuclear power station accident of Chernobyl. Immediately after the event (June - Aug. 86) both Cs 137 and Cs 134 were negative, with the exception of one sample. Increased levels of Cs 137 were found in the next three periods of measurement (Nov. 86 - Jan. 87), (June - Aug. 87), (March 88), with the highest results one year after the accident. Increased levels of Cs 134 were found only in the last two periods of measurement. In seminal plasma, both Cs 137 and Cs 134, were elevated in some samples. An influence on the results of IVF was not registered.

[The prevalence of alcoholism (abuse and dependence) in the state of Bremen]. / Uber die Prävalenz des alkoholismus (Alkoholmibetabrauch und Alkoholabhängigkeit) im Bundesland Bremen

UNLABELLED: An attempt was made to establish the prevalence of alcoholism in the State of Bremen in 1973. A sample of the adult population was sent a questionnaire. The selection of questions was based on the principles of the WHO definition of 1952 and on dependence on alcohol. Amount of drinks, behavior, psychosocial consequences and dependence on alcohol were gone into. The assessment of answers was weighted. RESULTS: When very strict criteria are applied, alcoholism existed among 2-2.5% of the population samples. With slightly less strict criteria which probably correspond more closely with reality, it was 3-4%. This, calculated for the whole population of Bremen, shows a prevalence of at least 1.6-2%, probably 2-3%. Alcoholism is not evenly distributed between sexes, age groups, social status and income-groups. The relation between men and women is 2 to 1. Most alcoholics are found among those aged 16-29 years and among unskilled workers, in the income group between 800 and 1399 DM p/month and among those not stating their income. The smallest number of alcoholics was in the group between 40 and 49 years old, among people not in top positions of the civil service or in business and in the lowest income group (less than DM 800 p/month). It is remarkable that no difference was found to be related to educational standards.