Mediastinal radiotherapy after multidrug chemotherapy and prophylactic cranial irradiation in patients with SCLC--treatment results after long-term follow-up and literature overview.

INTRODUCTION: Curative therapy for patients with small-cell lung cancer (SCLC) is based on multidrug chemotherapy combinations and radiotherapy. After a long time follow-up, the aim of the study was to evaluate the efficacy and toxicity of sequential chemo-radiotherapy and the effect of prophylactic cranial irradiation (PCI). METHODS: From 1995-2005, 96 patients with SCLC (64 limited-disease [LD], 32 extensive-disease [ED]; median age 61 years [range 39-79]) were treated at our department with varying chemotherapy regimens and sequential mediastinal radiotherapy (50 Gy + 10 Gy boost in case of residual disease after chemotherapy). Afterwards, 15 patients with LD, good general condition and at least partial response after local treatment received PCI (30 Gy). RESULTS: After a median follow-up of 78.6 months, 20 patients remained alive (20.8%, median survival time 18.2 months). The 2-/5-year overall survival rates were 33.8% and 12.6%, the 2-/5-year loco-regional control rates were 30.3% and 24.5%, respectively. Distant metastases occurred in 43 patients (24 cerebral). Cerebral metastasis occurred in 6.7% and 27.2% of the patients with PCI and without PCI respectively. Only tumor stage showed a statistically significant impact on overall survival and loco-regional control in multivariate analysis. Radiotherapy was well tolerated. Grade 3/4 toxicity occurred in seven patients. Prognosis of patients with SCLC remains poor. Administration of PCI in selected patients bears a decrease in the incidence of cerebral metastases. Alternative chemotherapy schemes as well as irradiation schemes and techniques should be the substance of future randomized trials.

[Radiotherapy : an option for refractory salivary fistulas]. / Radiatio : Therapieoption bei therapierefraktärer Speichelfistel.

A 45-year-old patient presented with refractory salivary fistula, attributed to multiple surgery and Botulinum toxin, following lateral parotidectomy. He underwent fractionated radiotherapy of the remaining parotid gland including the fistula opening (total dose of 30 Gy) at our clinic. In time, fistula secretion could be inhibited completely. Although the indication for radiotherapy for such fistulas is rare since Botulinum toxin has been in use, it should still be considered in refractory disease courses.

Effective diffusivities and mass fluxes in fungal biopellets.

Mass transport within biological aggregates is a key process that can determine overall turnover rates in submerged cultivations. A parameter commonly used for its description is the effective diffusion coefficient D(eff), which is highly dependent on biomass density and structure. Different approaches have been used to estimate or measure D(eff), yet the data still shows broad scattering. This study provides experimental data on effective diffusivities of oxygen within fungal pellets. A correlation is found with the hyphal gradient (dh/dr), which is a morphological parameter describing the structure of the pellet periphery. Furthermore, the dependency of D(eff) on fluid dynamic conditions at the pellet is investigated. The comparison of the results with data from literature clearly demonstrates the influence of the experimental methodology applied for determination of D(eff). Moreover, it is shown that while diffusion limitation of whole pellets is mainly a function of size, the influence of advection in the outer zone of pellets that is supplied with oxygen is actually rather high. Thus, it is concluded that the effective diffusion coefficient might not be sufficient for the description of mass transport within the pellet periphery for a broad range of realistic fluid dynamic conditions during cultivation. Nevertheless, although actual mass transport rates inside pellets are unknown, mass fluxes can be calculated on the basis of spatially resolved data of oxygen and biomass distribution within the pellet.

Optically controlled interparticle distance tuning and welding of single gold nanoparticle pairs by photochemical metal deposition.

We report on the in-situ controlled tuning of the particle gap in single pairs of gold nanodisks by photochemical metal deposition. The optically induced growth of nanodisk dimers fabricated by electron beam lithography leads to a decrease of the interparticle gap width down to 0 nm. Due to the increasing particle size and stronger plasmonic coupling, a smooth redshift of the localized surface plasmon (LSP) resonances is observed in such particle pairs during the growth process. The interparticle gap width, and hence the LSP resonance, can be tuned to any desired spectral position. The experimental results we obtain with this nanoscale fabrication technique are well described by the so-called plasmon ruler equation. Consequently, both the changes in particle diameter as well as in gap width can be characterized in-situ via far-field read-out of the optical properties of the dimers.

Histomorphological tumor regression grading of esophageal carcinoma after neoadjuvant radiochemotherapy: which score to use?

Histopathological tumor regression grade (TRG) has been shown to be a prognostic factor in patients with esophageal cancer after neoadjuvant radiochemotherapy (RCT). The system introduced by Mandard to group TRG (Cancer 1994;73:2680-2686) has been used to analyse and discuss its prognostic significance on survival in a single institution retrospective analysis: TRG 1 (complete regression) - TRG 5 (absence of regressive changes). Sixty patients with locally advanced (T3/4 or N1) adenocarcinoma or squamous cell carcinoma received cisplatin-based RCT. Three to four weeks later operation for curative intent was performed. Median follow-up was 17.7 months. Histopathological tumor stages were stage 0 in 17%, stage I in 10%, stage II in 60%, stage III in 12% and stage IVA in 1%. The 5-year overall survival (OS) rate was 35%. In univariate analysis, ypN-status and TRG correlated significantly with OS (P = 0.004, P = 0.0008, respectively). While OS of TRG 1 differed significantly from all other groups, no differences in OS between the other TRG groups were seen. Patients with complete tumor regression after neoadjuvant RCT showed a much better survival than patients with tumors that responded less to induction therapy. Further qualitative subdivision of tumor regression could not identify patient groups with significant differences in prognosis. After comparing our data with the literature, it is reasonable to consider classifying all patients into 'Complete tumor regression' and 'Incomplete tumor regression'.

A comparison of three-field and four-field techniques in different clinical target volumes in prostate cancer irradiation using dose volume histograms: a prospective three-dimensional analysis.

The purpose of the current study was to quantitatively assess differences between irradiation techniques on normal tissue exposure in different clinical target volumes (CTVs) in irradiation of prostate cancer. 14 patients with prostate cancer undergoing external beam radiotherapy were investigated. The prostate and prostate + proximal/entire seminal vesicles were delineated as CTVs. A three-field and two different four-field plans were generated and compared concerning rectum, bladder and femoral head dose-volume histograms (DVHs). The exposure of the rectum exposed to 40-60 Gy was significantly lower for all CTVs with the three-field technique compared with both four-field techniques. The exposure of the rectum to 70 Gy was significantly lower for all CTVs with the weighted four-field technique compared with the unweighted four-field and three-field techniques. The weighted four-field technique was worst in bladder dose sparing for the three CTVs. Comparing the three-field and the unweighted four-field technique for irradiation of the prostate and prostate + entire seminal vesicles, no technique provided a clear advantage or disadvantage in bladder dose sparing. For irradiation of the prostate + proximal seminal vesicles the unweighted four-field technique provided the best bladder dose sparing. Concerning the exposure of the femoral heads, the three-field technique was significantly worse for the three CTVs compared with both four-field techniques. No difference was found between the unweighted and the weighted four-field techniques. In conclusion, none of the studied techniques consistently proved superior in different CTVs in prostate cancer irradiation with respect to sparing all organs at risk. The absolute differences between the three techniques were small and the clinical relevance of these findings is uncertain.

Medium term results in keratoprostheses with biocompatible and biological haptic.

PURPOSE: Corneal grafts or limbal stem cell transplantation are often unsuccessful in patients with severe ocular surface disorders such as severe dry eye syndrome, symblepharon or diffuse vascularisation. In those patients, a keratoprosthesis (KPro) may be an alternative for the recovery of vision. Various KPro differ from each other in the material of the haptic that supports the optic cylinder. The haptic may be made of biocompatible or biological material such as tibia bone (TKPro) or dentine and alveolar bone (osteo-odonto-keratoprosthesis, OOKP). On the basis of our experience, we wanted to comment on the value of different KPro. METHODS: Over the last 10 years we have implanted a total of 35 KPro, 29 with biological haptic (25 OOKP and four TKPro), and six KPro with biocompatible haptic (one Legais KPro, five Pintucci KPro). A follow up examination was carried out approximately every6 months. RESULTS: The patients gained a visual acuity of > or =0.9 in 20.6%, of > or =0.5 in 52.9%, of > or =0.2 in 61.8% and a significant improvement in visual acuity in 76.5%, respectively. There was no significant difference between the various types of KPro concerning the best postoperative visual acuity. All patients showing poor improvement had a pre-existing end stage secondary glaucoma or other retinal damage. The median follow-up was 2.9 years (maximum 8) for OOKP, 1 year for TKPro, 1 year (maximum 2) for Pintucci Kpro and 6 month for Legeais KPro. During this period, only one of the KPro with biological haptic was lost (one TKPro after 1 year), compared with four out of six of the KPro with biocompatible haptic (P<0.0001). CONCLUSIONS: Fixation of the KPro by a root of the patient s own tooth (OOKP) leads to the best results in the long-term follow up, as our results as well as the literature demonstrate. As long as a KPro is in place, the visual acuity is as good as the retinal function. For the ranking of different types of KPro, the percentage and the duration of the anatomic success are most important. The comparability of the various KPro results may be limited, since the patients were not randomised and the four groups differ in number.

Oxygen profiles and biomass distribution in biopellets of Aspergillus niger.

Morphology of fungal pellets has a significant influence on mass transfer and turnover processes in submerged cultures. There are many reports in literature that biomass is not distributed homogeneously over the pellet radius, yet quantitative data is rare. This study presents a method for the quantification of fungal pellet structure (Aspergillus niger). Confocal laser scanning microscopy (CLSM) is used in combination with image analysis freeware (Image J). Hyphal distribution is resolved spatially in radial direction. Quantitative morphological parameters are derived from digital images especially from the peripheral regions of the pellet that are not oxygen limited. This morphological information is combined with data of microelectrode measurements in the same pellets. Results show that the morphological parameters obtained can describe the impact of pellet structure on oxygen gradients much better than average biomass density. It is concluded that CLSM and image analysis are powerful tools not only to generate valuable data for quantitative description of pellet morphology. In addition, this data may be used in mathematical models to improve predictions of mass transfer and substrate conversion in mycelial aggregates.

[Development of cell content and shedding of Prototheca spp. in milk from infected udder quarters of cows]. / Entwicklung von Zellgehalt und Ausscheidung von Prototheca spp. in der Milch infizierter Euterviertel von Kühen.

It was the objective of this study to analyse shedding patterns and somatic cell counts in cows and quarters infected with Prototheca spp. and to evaluate two approaches to identify infected animals by somatic cell count (SCC) or by bacteriological analysis of pooled milk samples. Five lactating dairy cows, chronically infected with Prototheca spp. in at least one quarter were studied over 11 weeks to 13 months. Quarter milk samples and a pooled milk sample from 4 quarters were collected aseptically from all quarters of the cows on a weekly basis. Culture results of quarter milk and pooled samples were compared using cross tabulation. SCC of quarter milk samples and of pooled samples were related to the probability of detection in the infected quarters and cows, respectively. Shedding of Prototheca spp. was continuous in 2 of 8 quarters. In the other quarters negative samples were obtained sporadically or over a longer period (1 quarter). Overall, Prototheca spp. were isolated from 83.6% of quarter milk samples and 77.0% of pooled milk samples of infected quarters and cows. Somatic cell counts were higher in those samples from infected quarters that contained the algae than in negative samples (p < 0.0001). The same applied for composite samples from infected cows. Positive samples had higher SCC than negative samples. However, Prototheca spp. were also isolated from quarter milk and pooled samples with physiological SCC (i.e. < 10(5)/ml). Infected quarters that were dried off did not develop acute mastitis. However, drying off had no effect on the infection, i.e. samples collected at calving or 8 weeks after dry off still contained Prototheca spp. Results indicate that pre-selection of cows to be sampled for Prototheca spp. by SCC and the use of composite samples are probably inadequate in attempts to eradicate the disease. However, due to intermittent shedding of the algae in some cows, single herd sampling using quarter milk samples probably also fails to detect all infected cases. Therefore, continuous monitoring of problem cows with clinical mastitis or increased SCC in herds during eradication programs is recommended.

Concurrent low-dose cisplatin and thoracic radiotherapy in patients with inoperable stage III non-small cell lung cancer: a phase II trial with special reference to the hemoglobin level as prognostic parameter.

PURPOSE: To evaluate the efficacy of concurrent radiochemotherapy in patients with stage III non-small cell lung cancer (NSCLC), and to examine the effect of hemoglobin levels on survival of those patients. The negative impact of anemia on survival has been noticed for other cancer sites including the head and neck, and the uterine cervix, but it has been rarely described in NSCLC cancer patients treated with radiotherapy. METHODS: From April 1995 through March 2002, 56 patients with inoperable stage III non-small lung cancer were treated with radiotherapy consisting of 60 Gy (50 Gy+10 Gy boost) given in 30 fractions of 2 Gy daily, 5 days a week, over a period of 6 weeks, and concurrent low-dose daily chemotherapy (CHT) consisting of 6 mg/m(2) of cisplatin given Mondays-Fridays during weeks 1-2 and 5-6. All patients had stage III disease and ages ranged from 39 to 81 years old (median 63.9 years). RESULTS: The 2-year and 3-year survival rates were 34% and 16%, respectively. Patients with a pretreatment hemoglobin level superior or equal to 11.6 g/dl had a 2-year survival rate of 52% as compared to 15.5% for patients with a pretreatment hemoglobin level inferior to 11.6 g/dl (p=0.0075). Patients with higher KI (>70%) showed better survival rates than those with lower KI. Surprisingly, patients in stage IIIA did not survive significantly longer than those in stage IIIB. Hematological toxicity (grade > or =2) prevailed (25%), followed by esophageal (5.4%) and bronchopulmonary (2%) toxicity. Only three patients experienced acute grade 3 hematological toxicity. Because of acute toxic effects, irradiation was interrupted in 8 patients (14.3%) for 7-13 days (median 7.5 days). Late high-grade (> or =3) toxicity was not found. No grade 4 toxicity or treatment-related deaths were observed during this study. CONCLUSION: Our data show that concurrent radiotherapy with daily low dose cisplatin is well tolerated, and shows survival rates comparable to more aggressive treatment regimens. A combination of this chemotherapy with accelerated hyperfractionated radiotherapy might improve the results in the future. Furthermore, we could show that the hemoglobin levels prior to therapy have an influence on the prognosis, where lower levels were associated with worse outcome. Further trials should consider supplementation with erythropoietin.

[The Ahmed glaucoma valve. Medium term results]. / Die "Ahmed glaucoma valve" Mittelfristige Ergebnisse.

BACKGROUND: In complicated glaucoma, when classical filtrating surgery would be ineffective, aqueous shunts may be used. Complications due to hypotonia are reduced by valved systems, such as the Ahmed glaucoma valve (AGV). METHOD: In a retrospective case control study, 28 patients with complicated glaucoma were included. In addition to the clinical examination, we examined the size and function of the filtering area using ultrasound. RESULTS: The medium term follow-up was 25+/-16 months, the preoperative intraocular pressure (IOP) 35.5 mmHg+/-10.3 while 17 eyes were pseudophakic and nine aphakic. In the first weeks after AGV implantation, the mean IOP was 6.3+/-2.5 mmHg. In nine eyes, the pressure was less than 5 mmHg and five developed a temporary choroidal detachment. At the last visit, IOP was regulated in 22 eyes (82.1%). There was no correlation between IOP regulation and the size of the filtering bleb or the increase in the latter by digital pressure. CONCLUSION: In the management of complicated glaucoma, if there is a high risk of failure due to conjunctival scarring, AGV implantation can be used as a save procedure with a success rate comparable to other glaucoma implants.

Binding H2, N2, H-, and BH3 to transition-metal sulfur sites: synthesis and properties of [RuL(PR3)(N2Me2S2)] Complexes (L=eta2-H2, H-, BH3; R=Cy, iPr).

The reactions of [Ru(N(2))(PR(3))('N(2)Me(2)S(2)')] ['N(2)Me(2)S(2)'=1,2-ethanediamine-N,N'-dimethyl-N,N'-bis(2-benzenethiolate)(2-)] [1 a (R=iPr), 1 b (R=Cy)] and [micro-N(2)[Ru(N(2))(PiPr(3))('N(2)Me(2)S(2)')](2)] (1 c) with H(2), NaBH(4), and NBu(4)BH(4), intended to reduce the N(2) ligands, led to substitution of N(2) and formation of the new complexes [Ru(H(2))(PR(3))('N(2)Me(2)S(2)')] [2 a (R=iPr), 2 b (R=Cy)], [Ru(BH(3))(PR(3))('N(2)Me(2)S(2)')] [3 a (R=iPr), 3 b (R=Cy)], and [Ru(H)(PR(3))('N(2)Me(2)S(2)')](-) [4 a (R=iPr), 4 b (R=Cy)]. The BH(3) and hydride complexes 3 a, 3 b, 4 a, and 4 b were obtained subsequently by rational synthesis from 1 a or 1 b and BH(3).THF or LiBEt(3)H. The primary step in all reactions probably is the dissociation of N(2) from the N(2) complexes to give coordinatively unsaturated [Ru(PR(3))('N(2)Me(2)S(2)')] fragments that add H(2), BH(4) (-), BH(3), or H(-). All complexes were completely characterized by elemental analysis and common spectroscopic methods. The molecular structures of [Ru(H(2))(PR(3))('N(2)Me(2)S(2)')] [2 a (R=iPr), 2 b (R=Cy)], [Ru(BH(3))(PiPr(3))('N(2)Me(2)S(2)')] (3 a), [Li(THF)(2)][Ru(H)(PiPr(3))('N(2)Me(2)S(2)')] ([Li(THF)(2)]-4 a), and NBu(4)[Ru(H)(PCy(3))('N(2)Me(2)S(2)')] (NBu(4)-4 b) were determined by X-ray crystal structure analysis. Measurements of the NMR relaxation time T(1) corroborated the eta(2) bonding mode of the H(2) ligands in 2 a (T(1)=35 ms) and 2 b (T(1)=21 ms). The H,D coupling constants of the analogous HD complexes HD-2 a ((1)J(H,D)=26.0 Hz) and HD-2 b ((1)J(H,D)=25.9 Hz) enabled calculation of the H--D distances, which agreed with the values found by X-ray crystal structure analysis (2 a: 92 pm (X-ray) versus 98 pm (calculated), 2 b: 99 versus 98 pm). The BH(3) entities in 3 a and 3 b bind to one thiolate donor of the [Ru(PR(3))('N(2)Me(2)S(2)')] fragment and through a B-H-Ru bond to the Ru center. The hydride complex anions 4 a and 4 b are extremely Brønsted basic and are instantaneously protonated to give the eta(2)-H(2) complexes 2 a and 2 b.

Binding N2, N2H2, N2H4, and NH3 to transition-metal sulfur sites: modeling potential intermediates of biological N2 fixation.

In the quest for low-molecular-weight metal sulfur complexes that bind nitrogenase-relevant small molecules and can serve as model complexes for nitrogenase, compounds with the [Ru(PiPr(3))('N(2)Me(2)S(2)')] fragment were found ('N(2)Me(2)S(2)'(2-)=1,2-ethanediamine-N,N'-dimethyl-N,N'-bis(2-benzenethiolate)(2-)). This fragment enabled the synthesis of a first series of chiral metal sulfur complexes, [Ru(L)(PiPr(3))('N(2)Me(2)S(2)')] with L=N(2), N(2)H(2), N(2)H(4), and NH(3), that meet the biological constraint of forming under mild conditions. The reaction of [Ru(NCCH(3))(PiPr(3))('N(2)Me(2)S(2)')] (1) with NH(3) gave the ammonia complex [Ru(NH(3))(PiPr(3))('N(2)Me(2)S(2)')] (4), which readily exchanged NH(3) for N(2) to yield the mononuclear dinitrogen complex [Ru(N(2))(PiPr(3))('N(2)Me(2)S(2)')] (2) in almost quantitative yield. Complex 2, obtained by this new efficient synthesis, was the starting material for the synthesis of dinuclear (R,R)- and (S,S)-[micro-N(2)[Ru(PiPr(3))('N(2)Me(2)S(2)')](2)] ((R,R)-/(S,S)-3). (Both 2 and 3 have been reported previously.) The as-yet inexplicable behavior of complex 3 to form also the R,S isomer in solution has been revealed by DFT calculations and (2)D NMR spectroscopy studies. The reaction of 1 or 2 with anhydrous hydrazine yielded the hydrazine complex [Ru(N(2)H(4))(PiPr(3))('N(2)Me(2)S(2)')] (6), which is a highly reactive intermediate. Disproportionation of 6 resulted in the formation of mononuclear diazene complexes, the ammonia complex 4, and finally the dinuclear diazene complex [micro-N(2)H(2)[Ru(PiPr(3))('N(2)Me(2)S(2)')](2)] (5). Dinuclear complex 5 could also be obtained directly in an independent synthesis from 1 and N(2)H(2), which was generated in situ by acidolysis of K(2)N(2)(CO(2))(2). Treatment of 6 with CH(2)Cl(2), however, formed a chloromethylated diazene species [[Ru(PiPr(3))('N(2)Me(2)S(2)')]-micro-N(2)H(2)[Ru(Cl)('N(2)Me(2)S(2)CH(2)Cl')]] (9) ('N(2)Me(2)S(2)CH(2)Cl'(2-) =1,2-ethanediamine-N,N'-dimethyl-N-(2-benzenethiolate)(1-)-N'-(2-benzenechloromethylthioether)(1-)]. The molecular structures of 4, 5, and 9 were determined by X-ray crystal structure analysis, and the labile N(2)H(4) complex 6 was characterized by NMR spectroscopy.

Drainage devices in glaucoma surgery.

Glaucoma drainage devices, also termed aqueous shunts (AS), are widely used in the USA. Indications for AS include excessive conjunctival scarring diminishing the success of another filtration surgeries, abnormalities of the iridocorneal angle, neovascular glaucoma, presence of corneal grafts, and inflammatory glaucoma. Qualified success has been achieved for many years in 50 to 100 % of the treated eyes, depending on the patient selection. An AS consists of a silicone tube that is inserted into the anterior chamber and a plate (explant) made of silicone or polypropylene. The latter is positioned between the recti muscles. Within some weeks the surrounding tissue forms a fibrous bleb around the plate. This serves as a permanent filtration reservoir. The most serious complication is postoperative hypotonia, that can lead to serious choroidal detachment, suprachoroidal hemorrhage, anterior chamber flattening, and corneal decompensation. To avoid this complication some devices, e.g. the Ahmed Glaucoma valve and the Krupin valve, have integrated mechanisms to sustain a residual intraocular pressure. With other devices such as the Molteno and the Baerveldt devices the tube has to be temporarily ligated until a scar area forms around the explant. On the other hand, fibrous infiltration of the wall of the bleb often leads to a reversible rise in intraocular pressure about one to four months after surgery which can be treated by massaging the bulb, needling the bleb, or injection of antimetabolites. There are no obvious differences between the different AS regarding the success of pressure control. With appreciation of indications and therapy of complications, AS are an useful option in the management of complicated glaucoma, where conventional filtration surgery is considered to carry a high risk of failure.

An RAPD (random amplified polymorphic DNA) analysis of genetic population structure of Balea biplicata (Gastropoda: Clausiliidae) in fragmented floodplain forests of the Elster/Saale riparian system.

Eight German populations of the land snail Balea biplicata (Mollusca: Clausiliidae) were studied using the randomly amplified polymorphic DNA-polymerase chain reaction and morphometrics (principal component and discriminant analysis) to examine population structure and gene flow patterns in a fragmented landscape mosaic along the Elster/Saale riparian system, Germany. A variety of population genetic analyses targeting either more on the geographic scale of gene flow (genetic distances, F statistics, Mantel test) or on local genotypic structure (heterozygosity, linkage disequilibrium, bottleneck probability) showed that (1) the population system in total is governed by high gene flow independent of geographic distance, (2) genetic structure on the narrower sampling scale is mainly determined by stochastic processes due to genetic drift in small isolated and frequently recolonized populations, and (3) the morphometrical variation of the populations was related neither to habitat nor to genetic heterogeneity. The potentials for active and passive dispersal capacity of the snails and possible environmental impacts on their population structure are discussed.

Effect of keratinocyte growth factor on the proliferation, clonogenic capacity and colony size of human epithelial tumour cells in vitro.

PURPOSE: The effect of recombinant human keratinocyte growth factor (rHuKGF) on the proliferation, clonogenic capacity and colony size of low-passage human epithelial tumour cells was tested in vitro. MATERIALS AND METHODS: Five tumour cell cultures derived from head and neck squamous cell carcinomas, three cultures derived from pleural effusions of carcinomas of different origin and normal human nasal epithelial cells were analysed in passages 2-4. Expression of FGF7 and its receptor (FGFR2) were determined by the RNase protection assay. Cells were incubated with rHuKGF (10-200 ng ml(-1)) 3 days before or immediately after plating for clonal growth in serum-depleted media. To determine cellular radiosensitivity, single doses of 1-8 Gy X-rays were applied. Colony formation as well as colony size, reflecting the number of cell divisions, was determined after 10-15 days of growth in rHuKGF-treated and control cells. RESULTS: Normal nasal epithelial cells showed a two- to threefold increase in the number of cell divisions due to rHuKGF-treatment. In tumour cell cultures, significant stimulation of proliferation occurred in only one of eight samples. Tumour cells expressed FGF7 mRNA and protein, and low levels of FGFR2 mRNA. The addition of rHuKGF to the medium of the tumour cell cultures influenced neither radiation-induced impairment of proliferation nor clonogenic cell survival. CONCLUSION: rHuKGF has been shown to ameliorate the radiation tolerance of normal epithelia. The minimum in vitro tumour cell response to rHuKGF compared with normal epithelial cells suggests a potential for selective protection of normal epithelia during radiotherapy. The low FGFR2 expression as well as the FGF7 expression in the tumour cells may contribute to their resistance to rHuKGF treatment.

[Drainage systems in glaucoma surgery]. / Drainagesysteme in der Glaukomchirurgie.

Glaucoma drainage devices, also known as aqueous shunts (AS) are widely used in the USA. They consist of a silicone tube that is inserted into the anterior chamber and connected to a plate made of silicone or polypropylene, the explant. The latter is positioned between the recti muscles and over several weeks the surrounding tissue forms a fibrous bleb around the plate. This serves as a permanent filtration reservoir.Recurrent failure of filtrating surgery is the main indication for the use of AS. Other indications include situations in which the formation of a filtering bleb seems to be unpromising because of extensive conjunctival scarring. Qualified success has been achieved for many years in 50-100% of the eyes treated depending on patient selection. The most serious complication is postoperative hypotonia that can lead to serious chorioidal detachment, suprachorioidal hemorrhage, flat anterior chamber and corneal decompensation. To avoid this complication some devices, i.e.the Ahmed Glaucoma and the Krupin valve have integrated mechanisms to sustain a residual intraocular pressure. With other devices i.e. the Molteno and the Baerveldt devices, the tube has to be temporarily ligated until bleb formation has started. On the other hand fibrous infiltration of the bleb 1-4 months after the surgery often leads to a reversible rise in introcular pressure, which can be treated by massaging the bulbus, needling the bleb or injection of antimetabolites. There are no obvious differences between the various forms of AS with regard to the success of pressure regulation. In summary,by close scrutiny of indications and management of complications,drainage systems are a useful option in the management of complicated glaucoma that carry a high risk of failure from conventional filtering surgery.

Heterologous amplification of microsatellite markers from colubroid snakes in European natricines (serpentes: natricinae).

Eighteen microsatellite loci developed for a range of snake species (New World natricines, elapids, crotalids) were tested against European natricines (Natrix natrix, N. maura, and N. tessellata) in cross-species amplification experiments. Five loci were polymorphic (average expected heterozygosity 0.749 for a population of N. natrix in Amsterdam, mean sample size 47.8) and three loci were monomorphic. The remainder could not be consistently scored or failed to amplify. Further tests on single individuals of a diverse set of eight species of colubroid snakes showed that 15 of the 18 loci could be cross-amplified in at least one of these species. We conclude that our results show promise for the utilization of these markers for experimental assessments of genetic variation in the phylogenetically closely related group of European natricine snakes with emphasis on N. natrix. The full suite of microsatellite markers now available for snakes may show additional potential for subsequent investigation across a broader range of colubroid snakes.

Monitoring of therapy in head and neck patients during the radiotherapy by measurement of Cyfra 21-1.

PURPOSE: Cyfra 21-1, measuring serum fragments of cytokeratin 19, has been found to be related to tumour stage and tumour size in patients with cervical cancer. It could be a promising marker in squamous lung cancer. We evaluated this new marker with carcinoembryonic antigen, (CEA) and squamous cell carcinoma antigen (SCC-Ag) in the monitoring of 27 patients with head and neck cancer. PATIENTS AND METHODS: The retrospective study group consisted of 27 patients, 17 not suited for surgery and 10 after laser resection. Patients were clinically staged according to the TNM-classification. The mean age of the patients was 53 years (range 37-70 years). Serum levels of each marker were studied in relation to tumour stage and clinical status of the patients during radiotherapy and 6 weeks after the end of the treatment. The clinical performance of the various assays to separate those patients with complete remission from those patients with the presence of tumour was assessed. RESULTS: Pre-treatment serum Cyfra 21-1, CEA, and SCC-Ag levels were not related to stage of disease and were not found to be predictive of tumour response. The clinical performance of post-treatment serum SCC-Ag levels in predicting the presence of tumour was not better than the Cyfra 21-1 assays. CONCLUSION: We could not conclude from this study that Cyfra 21-1 marker is an additional parameter in identifying patients at risk of residual tumour after treatment, recurrent or progressive disease. An elevation of cyfra 21-1 marker was not detectable in 70% of the cases with macroscopic tumour. Therefore, Cyfra 21-1 is not a reliable parameter for the monitoring of patients with head and neck cancer during radiotherapy.