Uso de un gel polimérico para evitar retropulsión durante la litotricia intracorpórea / Use of a Polymeric Gel to Prevent Retropulsion During Intracorporeal Lithotripsy

Introducción: La retropulsión de los cálculos durante la litotricia ureteroscópica puede conducir a procedimientos adicionales necesarios para los cálculos residuales. Se han introducido varios dispositivos en un intento de reducir la retropulsión. Nos pusimos en marcha para informar de nuestra experiencia inicial al utilizar el nuevo gel polimérico BackStop®. Material y métodos: Hemos recogido de forma prospectiva los datos sobre 7 procedimientos de ureteroscopia con cálculos ureterales distales tratados con BackStop®. Se recogieron los datos perioperatorios, tales como tamaño del cálculo, ubicación, tiempo quirúrgico, tasa libre de cálculo, presencia o ausencia de retropulsión. El éxito se definió como la ausencia de fragmentos residuales, de retropulsión y de procedimientos adicionales que se requieren. Resultados: Todos los pacientes quedaron libres de litiasis tras la URS y no se produjo ninguna retropulsión. No hubo complicaciones intraoperatorias ni migración de gel o problemas con la disolución del gel. Conclusiones: BackStop® es un nuevo tratamiento prometedor para prevenir la retropulsión durante la litotricia intracorpórea ureteral. Es seguro, fácil de aplicar y muy eficaz en la prevención de la migración de fragmentos de cálculos. Backstop® tiene el potencial para reducir el tiempo quirúrgico (AU)

Introduction: Stone retropulsion during ureteroscopic lithotripsy may lead to additional procedures needed for residual calculi. Several devices have been introduced in an attempt to reduce retropulsion. We set out to report our initial experience utilizing the new polymeric gel, BackStop®. Material and methods: We prospectively collected data on 7 ureteroscopy procedures with distal ureteral calculi treated with BackStop®. Perioperative data including stone size, location, operative time, stone free rate, the presence or absence of retropulsion was collected. Success was defined as no residual fragments, no retropulsion, and no additional procedures required. Results: All of the patients were rendered stone free after URS and no retropulsion occurred. There were no intraoperative complications nor gel migration or problems with dissolving the gel. Conclusions: BackStop® is a new promising therapy to prevent retropulsion during ureteral intracorporeal lithotripsy. It is safe, easy to apply and very effective in preventing stone fragment migration. BackStop® has the potential to reduce operative time (AU)

A novel continuous powder aerosolizer (CPA) for inhalative administration of highly concentrated recombinant surfactant protein-C (rSP-C) surfactant to preterm neonates.

BACKGROUND: In pulmonary medicine, aerosolization of substances for continuous inhalation is confined to different classes of nebulizers with their inherent limitations. Among the unmet medical needs is the lack of an aerosolized surfactant preparation for inhalation by preterm neonates, to avoid the risks associated with endotracheal intubation and surfactant bolus instillation. In the present report, we describe a high-concentration continuous powder aerosolization system developed for delivery of inhalable surfactant to preterm neonates. METHODS: The developed device uses a technique that allows efficient aerosolization of dry surfactant powder, generating a surfactant aerosol of high concentration. In a subsequent humidification step, the heated aerosol particles are covered with a surface layer of water. The wet surfactant aerosol is then delivered to the patient interface (e.g., nasal prongs) through a tube. RESULTS: The performance characteristics of the system are given as mass concentration, dose rate, and size distribution of the generated aerosol. Continuous aerosol flows of about 0.84 L/min can be generated from dry recombinant surfactant protein-C surfactant, with concentrations of up to 12 g/m(3) and median particle sizes of the humidified particles in the range of 3 to 3.5 µm at the patient interface. The system has been successfully used in preclinical studies. CONCLUSION: The device with its continuous high-concentration delivery is promising for noninvasive delivery of surfactant aerosol to neonates and has the potential for becoming a versatile disperser platform closing the gap between continuously operating nebulizers and discontinuously operating dry powder inhaler devices.

Unexpected brain lesions in lactating Sprague-Dawley rats in a Two-generation Inhalation Reproductive Toxicity Study with pentafluoropropane (HFC-245fa).

The study presented was conducted following the reproductive study guideline OECD Guideline 416 Two-Generation Reproduction Toxicity Study. Sprague-Dawley rats were exposed to 2000, 10,000 and 50,000 ppm of HFC-245fa. There was an unexpected mortality of lactating dams in the medium and high dose group beginning at day 10 of lactation. Statistically significant histopathological alterations were observed in the cerebellum of a total of 9/30 females of the high dose group of the F0-generation and in 10/27 females of the high dose group of the F1-generation. In contrast there were no brain lesions found in males or non-pregnant females of all dose groups. Neuronal necrosis and degeneration in the cerebellar cortex were observed as the most severe finding. Furthermore vacuolation of the neuropil in different degrees was diagnosed in 7/30 females of the F0-generation and in 9/30 females of the F1-generation. Acute hemorrhages - in particular perivascular - occurred in 5/30 females of the F0- and in 5/30 females of the F1-generation indicating a disturbed vascular integrity. The main lesions found in the cerebrum were glial scars in the corpus callosum and restricted to 2/30 females of the F0-generation of the high dose group. The increased incidence of myocardial fibrosis and mononuclear cell infiltration in males - indicating myocarditis - was only seen in the F0-generation of the high dose group. Females of the F1-generation of the high dose group showed an increased incidence of minimal myocardial fibrosis. In summary, histopathology revealed that the brain, particularly the cerebellum, and to a minor degree the heart turned out to be the toxicological target organs of the substance. Presumably substance-related energy deprivation may be responsible for the observed changes. One of the metabolites, 3,3,3-trifluoropropanoic acid has been shown to be capable of causing this effect.

[Use of a polymeric gel to prevent retropulsion during intracorporeal lithotripsy]. / Uso de un gel polimérico para evitar retropulsión durante la litotricia intracorpórea.

INTRODUCTION: Stone retropulsion during ureteroscopic lithotripsy may lead to additional procedures needed for residual calculi. Several devices have been introduced in an attempt to reduce retropulsion. We set out to report our initial experience utilizing the new polymeric gel, BackStop. MATERIAL AND METHODS: We prospectively collected data on 7 ureteroscopy procedures with distal ureteral calculi treated with BackStop. Perioperative data including stone size, location, operative time, stone free rate, the presence or absence of retropulsion was collected. Success was defined as no residual fragments, no retropulsion, and no additional procedures required. RESULTS: All of the patients were rendered stone free after URS and no retropulsion occurred. There were no intraoperative complications nor gel migration or problems with dissolving the gel. CONCLUSIONS: BackStop is a new promising therapy to prevent retropulsion during ureteral intracorporeal lithotripsy. It is safe, easy to apply and very effective in preventing stone fragment migration. BackStop has the potential to reduce operative time.

The non-intubated, spontaneously breathing, continuous positive airway pressure (CPAP) ventilated pre-term lamb: a unique animal model.

Neonatologists prefer non-invasive ventilation methods for pre-term neonates, who often require surfactant treatment. Therefore, a technology for non-invasive surfactant administration would be highly appreciated. We have developed a Continuous Powder Aerosolization (CPA) system for the generation of a humidified recombinant surfactant protein-C (rSP-C) surfactant aerosol for non-invasive administration to pre-term neonates via bi-nasal prongs. Before conducting clinical trials, safety testing in an adequate pre-clinical animal model is necessary. In contrast to existing pre-term lamb models, this model should use non-intubated animals to include upper airways for safety testing. Pre-term animals should have already a sufficient respiratory drive to breathe spontaneously on non-invasive continuous positive airway pressure (CPAP) support, but their lungs should still be pre-mature to be comparable with the clinical situation for the treatment of pre-term infants. The aim of this feasibility study was therefore to establish a CPAP-stable, non-intubated pre-term lamb model for the investigation of safety, efficacy, and pulmonary deposition of a humidified rSP-C surfactant aerosol. For this purpose, 19 pre-term lambs with a gestational age of 135-137 days (term: about 144 days) were delivered via Caesarean section. Four animals died before start of treatment, while the remaining animals were treated via customized bi-nasal prongs with rSP-C surfactant aerosol or humidified air as vehicle control. To determine pulmonary deposition, selected animals received rSP-C surfactant labelled with samarium oxide as non-radioactive tracer. Treatment was started at 30 min of age and was continued for 1 or 2.5 h. Investigations during the in-life phase included observation of clinical signs, haematology, blood gas analysis, and determination of minute volume. At 3 h of age, animals were euthanized and organs removed for histopathology investigation or for determination of pulmonary deposition. Administration of humidified, aerosolized rSP-C surfactant was well tolerated, and histopathology investigation of upper airways and lungs revealed no aerosol-related changes. Mean body weight-corrected pulmonary deposition of rSP-C surfactant ranged from 1.7 to 7.7 mg/kg depending on the duration of treatment and aerosolization parameters used. A trend towards reduced spontaneous minute volumes indicating reduced breathing efforts and towards reduced lung weights indicating less fluid in the lungs of surfactant-treated animals compared to animals of the vehicle control group could be seen. Taken together, a CPAP-stable, non-intubated pre-term lamb model was successfully established and the parameters for the investigation of safety, efficacy, and pulmonary deposition of aerosolized rSP-C surfactant for the subsequent main study were identified.

Evaluation of reproductive/developmental and repeated dose (subchronic) toxicity and cytogenetic effects in rats of a roofing asphalt fume condensate by nose-only inhalation.

A Type III Built-up Roofing Asphalt (BURA) fume condensate was evaluated for subchronic systemic toxicity and reproductive/developmental toxicity screening in Wistar rats, by OECD protocol 422 and OECD cytogenetic protocol 474. Animals were exposed by nose-only inhalation to target concentrations of 30, 100 and 300 mg/m³ total hydrocarbons (actual concentrations, 30.0, 100.1 and 297.3 mg/m³). The study was performed to assess potential hazards from asphalt fumes to which humans could be exposed during application. No adverse effects were seen for spermology, reproductive or developmental parameters or early postnatal development of offspring from day 1 to 4 postpartum. BURA fume condensate did not induce any significant increases in micronucleus frequency in polychromatic erythrocytes of rat bone marrow nor was neurobehavioral toxicity observed at any dose. Systemic effects were slight and seen at doses above those measured at work sites. The systemic NOAEC of 100 mg/m³ for males was based on decreased body weight gain, food consumption and increased absolute and relative lung wet weight correlated with slight histological changes in the lung, primarily adaptive in nature at 300 mg/m³. The female NOAEC of 30 mg/m³ was based on a statistically significant increase in relative wet lung weight at higher doses, correlated with slight histopathologic effects in the lungs at the highest dose. However, no increase in relative lung weight was seen in breeding females at 100 mg/m³.

A toxicological evaluation of inhaled solid lipid nanoparticles used as a potential drug delivery system for the lung.

Inhalation is a non-invasive approach for both local and systemic drug delivery. This study aimed to define the therapeutic window for solid lipid nanoparticles (SLNs) as a drug delivery system by inhalation from a toxicological point of view. To estimate the toxic dose of SLNs in vitro, A549 cells and murine precision-cut lung slices (PCLS) were exposed to increasing concentrations of SLNs. The cytotoxic effect of SLNs on A549 cells was evaluated by MTT and NRU assays. Viability of lung tissue was determined with WST assay and by life/dead staining using calcein AM/EthD-1 for confocal microscopy (CLSM) followed by quantitative analysis with IMARIS. Inflammation was assessed by measuring chemokine KC and TNF-alpha levels. The in vivo effects were determined in a 16-day repeated-dose inhalation toxicity study using female BALB/c mice, which were daily exposed to different concentrations of SLN30 aerosols (1-200 microg deposit dose). Local inflammatory effects in the respiratory tract were evaluated by determination of total protein content, LDH, chemokine KC, IL-6, and differential cell counts, performed on days 4, 8, 12, and 16 in bronchoalveolar lavage fluid. Additionally, a histopathological evaluation of toxicologically relevant organs was accomplished. The in vitro and ex vivo dose finding experiments showed toxic effects beginning at concentrations of about 500 microg/ml. Therefore, we used 1-200 microg deposit doses/animal for the in vivo experiments. Even after 16 days of challenge with a 200-microg deposit dose, SLNs induced no significant signs of inflammation. We observed no consistent increase in LDH release, protein levels, or other signs of inflammation such as chemokine KC, IL-6, or neutrophilia. In contrast, the particle control (carbon black) caused inflammatory and cytotoxic effects at corresponding concentrations. These results confirm that repeated inhalation exposure to SLN30 at concentrations lower than a 200-microg deposit dose is safe in a murine inhalation model.

Ex vivo lung function measurements in precision-cut lung slices (PCLS) from chemical allergen-sensitized mice represent a suitable alternative to in vivo studies.

A wide range of industrial chemicals can induce respiratory allergic reactions. Hence, there is an urgent need for methods identifying and characterizing the biological action of chemicals in the lung. Here, we present an easy, reliable alternative method to measure lung function changes ex vivo after exposure to chemical allergens and compare this to invasive in vivo measurements after sensitization with the industrial chemicals trimellitic anhydride (TMA) and 2,4-dinitrochlorobenzene (DNCB). Female BALB/c mice were sensitized epicutaneously with the respiratory allergen TMA and the contact sensitizer DNCB. The early allergic response to TMA and DNCB was registered in vivo and ex vivo on day 21 after inhalational challenge with dry standardized aerosols or after exposure of precision-cut lung slices (PCLS) to dissolved allergen. Airway hyperresponsiveness (AHR) to increasing doses of methacholine (MCh) was measured on the next day in vivo and ex vivo. Bronchoalveolar lavage (BAL) was performed for immunological characterization of local inflammation. TMA-sensitized mice showed AHR to MCh in vivo (ED(50): 0.06 microg MCh vs. 0.21 microg MCh in controls) and in PCLS (EC(50): 0.24 microM MCh vs. 0.4 microM MCh). TMA-treated animals showed increased numbers of eosinophils (12.8 x 10(4) vs. 0.7 x 10(4)) and elevated eotaxin-2 concentrations (994 pg/ml vs. 167 pg/ml) in BAL fluid 24 h after allergen challenge. In contrast, none of these parameters differed after sensitization with DNCB. The present study suggests that the effects of low molecular weight allergens, like TMA and DNCB, on ex vivo lung functions tested in PCLS reflect the in vivo situation.

Collection, validation and generation of bitumen fumes for inhalation studies in rats Part 3: Regeneration of bitumen fumes, inhalation setup, validation.

Undertaking a chronic inhalation study on bitumen fume presents a challenge in terms of generating sufficient amounts of representative fume. The objective of the study described in this and in previous publications was to collect sufficient fume and use this to develop a laboratory-generated exposure atmosphere, for use in chronic inhalation toxicity studies in rats that resembles, as closely as possible, personal exposures seen in workers during road paving operation. To achieve this goal, atmospheric workplace samples were collected at road paving work sites and compared with bitumen fume condensate samples collected from the headspace of hot bitumen storage tanks. In Parts 1 and 2, we described the collection and analysis of workplace samples, the strategy for in-line extraction of a suitable fraction of bitumen fume collected from the headspace of a bitumen storage tank and the comparison of the collected condensate to the workplace samples. This paper (Part 3) describes the regeneration of bitumen fume for inhalation and the exposure setup used for inhalation studies.

Collection, validation and generation of bitumen fumes for inhalation studies in rats Part 1: Workplace samples and validation criteria.

OBJECTIVES: Undertaking a chronic inhalation study on bitumen fume presents a challenge in terms of generating large amounts of representative fume. The objective of the study described in this and the following contributions was to collect sufficient fume and develop a laboratory-generated exposure atmosphere that resembles, as closely as possible, personal exposures seen in workers during road paving operations, for use in chronic inhalation toxicity studies in rats. METHODS: To achieve this goal, atmospheric workplace samples were collected at road paving work sites both by Shell Global Solutions, Int. (Shell) and by the 'Berufsgenossenschaftliches Institut für Arbeitssicherheit' (BIA, Germany) and compared with bitumen fume condensate samples collected from the head space of hot bitumen storage tanks. Part 1 describes the collection and analysis of personal and static workplace samples. Different sampling methods were also used to allow a comparison of the standard German sampling method with the most common industry method used. Samples were analyzed by Shell, BIA and by the Fraunhofer Institute of Toxicology and Experimental Medicine (Fh-ITEM, Germany) using different methods. Parameters determined were: total particulate matter (TPM), benzene soluble matter (BSM), semi-volatiles (SV), total organic matter (TOM), boiling point distribution (BPD), polycyclic aromatic hydrocarbons (PAHs) and UV fluorescence (UVF). RESULTS: The BPD of personal and static samples had almost identical start and end points, but static samples show a tendency towards an increase in amounts of higher boiling point compounds. Personal samples generally show higher PAH concentrations than comparable static samples. The results of the analysis of personal workplace samples were used to establish validation/acceptance criteria for the bitumen fume condensate sampled from storage tanks for the inhalation study, which is described in a further publication. CONCLUSIONS: The criteria involve a range of parameters that can be analyzed in both workplace samples and samples of tank fume condensate: BPD, UVF and content of individual PAHs were selected as parameters.

Collection, validation and generation of bitumen fumes for inhalation studies in rats Part 2: Collection of bitumen fumes from storage tanks.

OBJECTIVES: The objective of the study described in this and an accompanying series of papers was to develop a laboratory generated exposure atmosphere to be used for chronic inhalation toxicity studies in rats that resembles, as closely as possible, personal exposures seen by workers during road paving operations. METHODS: To achieve this objective, atmospheric workplace samples were collected at road paving worksites and compared analytically with bitumen fume samples collected from the headspace of hot bitumen storage tanks. In Preiss et al. (2006) the collection and analysis of workplaces samples is described. This contribution describes the strategy for the in-line extraction of a suitable fraction of bitumen fume collected from the headspace of a bitumen storage tank and the comparison of the collected condensate to workplace samples. RESULTS: Results show that is possible to develop a collecting procedure that allows sampling from hot bitumen storage tanks in an operational asphalt mixing plant. The sampling procedure has been optimized to collect material that matches the workplace samples as closely as possible. The comparison to workplace samples has been performed using parameters that can be analyzed in both the workplace samples and the bitumen fume condensate collected from the tanks. Boiling point distribution (BPD), UV fluorescence (UV-Fl) and content of individual polycyclic aromatic hydrocarbons (PAH) were selected as parameters. The BPD of the final collected bitumen fume condensate did not differ by more than 17 degrees C from any point on the average BPD curve of the workplace samples, in the range from 5 to 95%. UV-Fl of the bitumen fume condensate nearly exactly matched the average UV-Fl of the workplace samples. However, the sum of the 17 PAHs analyzed in the test samples, compared to the mass of the condensate, is lower by a factor of approximately 3 than the sum of the 17 PAHs in some personal samples compared to the mass of Total Organic Matter (TOM). It has to be recognised that during the collection of the workplace samples, despite all efforts a number of the workers who carried a personal sampler could not be prevented from smoking.

The response of skin perfusion and of rheological and immunological variables to intravenous prostanoid administration in Raynaud's phenomenon secondary to collagenosis.

BACKGROUND: Prostanoids are used in the treatment of Raynaud's phenomenon and acral perfusion disorders secondary to collagenosis. In subjective terms, intravenous administration of these agents produces success in more than 50% of patients. The therapeutic outcome of clinical administration of alprostadil or iloprost may vary from individual to individual. PATIENTS AND METHODS: The following variables were analysed in a cross-over study in 27 patients with collagenosis and Raynaud's phenomenon: plasma viscosity and erythrocyte aggregation (rheological variables), partial pressure of oxygen and laser Doppler flowmetry in the finger region, and lymphocyte phenotyping and interleukin (IL) determinations (immunological variables). RESULTS: Laser Doppler flowmetry revealed significant differences between patients with secondary Raynaud's phenomenon and a control group of 25 healthy subjects. Laser Doppler readings did not change significantly as a result of the treatments. Therapy with iloprost produced a reduction in IL-1beta, L-selectin (CD 62 L) and IL-6. CONCLUSION: The change in immunological variables due to iloprost may explain the long-term effects of prostaglandins in the treatment of Raynaud's phenomenon. From our results it is not possible to infer any preference for iloprost or alprostadil.

[Occlusion of the arteries of the fingers after hyperextension trauma]. / Verschluss der Fingerarterien nach Uberstreckungstrauma.

Acute occlusion of digital arteries due to a sport injury A 33 year old female patient with acute ischaemia of the fingers I-II of the right hand was admitted to our emergency unit. She reported that this complete ischaemia had shortly occurred after a sport injury due to an extreme hyperflexion of the right hand in a volleyball match. Four days after this trauma she felt pain and paraesthesia in the right hand. Circular areas of ischaemia were developed with skin colour change to grey and dark blue. The primary measure of the blood pressure by doppler analysis showed no signals in the first and second finger. Initially she received 500 mg Aspirin by intravenous injection. The full therapeutic dose of LMWH related to the weight of the patient was given. On the basis of the short time interval between the occurrence of the symptoms and admission of the patient we decided to perform a so called retrograde intravenous injection. The aim of this therapy was the intraarterial lysis and reperfusion. The blood pressure in all fingers were nearly normal after three days. Daily intravenous transfusion of prostaglandin were given additionally. Necrosis could be prevented as a result of our treatment over seven days. At the end of our therapy only the skin epithelium of the second finger was slightly raised and showed a tendency to desquamation. All other fingers occurred in a normal colour.

Cross-fostering inhalation toxicity study with HCFC-123 in lactating Sprague-Dawley rats.

A study was performed in Sprague-Dawley rats (Crl:CD BR) to differentiate between effects of hydrofluorocarbon 123 (HCFC-123) on the lactating dam or on the fetus using fostering and cross-fostering of the offspring. Pregnant and/or lactating dams without the pups present were exposed to the test substance (1000 ppm) or clean air by whole-body inhalation for 6 h/day from day 6 to 19 post conceptionem (p.c.) and from day 5 to 21 post partum (p.p.). Pups were cross-fostered to new dams within the first 2 days after birth. Treatment of the mothers with HCFC-123 led to decreases in serum glucose, cholesterol, and triglycerides and increases in absolute and relative maternal liver weights. Decreased litter and individual pup weight and decreased serum triglycerides were observed in the pups of treated foster mothers. Treatment of the mothers with HCFC-123 did not influence milk production based on the body weight difference of the dam before suckling and 60 min after beginning of suckling using 12-pup "standard litters" of untreated dams. Total fat, glucose, and protein contents in the milk were also not influenced by the treatment. Trifluoroacetic acid (TFA), a main metabolite of HCFC-123, was observed in urine samples of standard litters that had been nursed by treated dams. In conclusion, the effects on offspring due to HCFC-123 treatment consisted of decreased pup weight and decreased serum triglycerides at weaning. All effects were due to treatment of the lactating dams, as no prenatally induced effects were found. Since milk production and nutritional constituents of the milk were not influenced, but significant amounts of the main metabolite were found in pup urine, an effect of HCFC-123 or its metabolite on the pups via maternal milk is considered to be a possible cause for their decreased weight gain.

Inhalation tolerance study for p-aramid respirable fiber-shaped particulates (RFP) in rats.

This study was designed to assess the lung clearance function in rats after subchronic exposure to p-aramid respirable fiber-shaped particulates (RFP). Male Wistar rats were exposed 6 hrs/day, 5 days/week for 3 months to 50, 200, and 800 RFP/ml measured by scanning electron microscopy (SEM). Recovery effects were followed up through 9 months postexposure. The retention of RFP (length > 5 microm) was about 25 x 10(6) RFPs per lung in the low dose group after 3 months of exposure. The corresponding values in the medium and high dose groups amounted to overproportionally higher values of 122 x 10(6) and 576 x 10(6) RFPs per lung, respectively. A decrease in the length of the retained RFPs over the 9-month recovery period was observed, indicating a breakage of long fibrils. Alveolar clearance half-times measured by gamma tracers indicated a dust overloading of lungs for the high dose group at 0 and 3 months postexposure. Bronchoalveolar lavage parameters revealed that p-aramid RFPs induced pronounced inflammatory effects in the high and medium dose groups. Histopathologically, slight fibrotic and hyperplastic lesions were observed in the medium and high dose groups directly after the end of exposure. The findings at the 3-month postexposure interval resulted in a reduction of inflammatory changes in the medium and high dose groups compared to the sacrifices upon cessation of exposure. No histopathologic effects were detected in the low dose group. In the high dose group the maximum functionally tolerated dose was exceeded. The No Observed Adverse Effect Level (NOAEL) of RFP was 50 RFP/ml as measured by SEM.

[Acute acral ischemia in all fingers possibly due to a Borrelia infection]. / Akute akrale Ischämie aller Finger als mögliche Folge einer Borrelieninfektion.

Acute interruption of circulation in the distal fingers can be both expression of an embolic event as well as the first manifestation of a vasculitis or collagenosis. The search for its cause is frequently difficult. In many cases a specialized analysis of the coagulation system as well as diagnostics such as ultrasound scan of the heart or a systematic antibody scanning do not reveal the origin of an embolus or the underlying disorder. On the basis of a case-report we would like to focus on a possible context between an infection of Borrelias stage III and consecutive deterioration of peripheral arterial perfusion in the fingers. Besides Jo-1- and positive sceleton-muscle-antibodies there were no serological and clinical indications for an autoimmune disease. It was possible to avoid acral necrosis by means of an antibiotic, immunosuppressive and rheological therapeutic concept. We recommend to control the borellia-antibody-level in cases of obscure threatening peripheral necrosis caused by arterial perfusion stop.

The arteriovenous impulse system in total hip arthroplasty.

BACKGROUND: Despite the continuing high incidence of deep vein thrombosis after total hip arthroplasty, currently available mechanical thromboprophylactic systems are not sufficiently utilised in Germany. PATIENTS AND METHODS: Duplex-sonographic measurements of the maximum venous flow velocity (V. femoralis) in 10 healthy individuals performed with a leg orientation synonymous to that during total hip arthroplasty were compared to figures obtained during an out-stretched leg position. Additionally, duplex-sonography was conducted on 9 patients intra-operatively during total hip replacement to complete the study. All investigations were executed both with and without application of the A-V Impulse System (AVIS), a mechanical thromboprophylactic procedure. RESULTS: In contrast to the out-stretched leg position, a decreased venous peak flow velocity during surgery as well as in the operation-identical leg orientation was demonstrated in the absence of AVIS. However, by means of AVIS, a significant increase in the venous peak flow velocity (p < 0.01) was achieved for both situations. Additionally, an increased vessel diameter of the V. femoralis communis was observed in 75% of patients due to the leg orientation stipulated for hip replacement surgery. CONCLUSION: The data suggest that the A-V Impulse System can effectively accelerate the venous reflux-flow during operations involving hip replacements and thus provide an early preventative therapy for deep vein thrombosis after a surgical procedure.

Micronucleus induction in V79 cells after direct exposure to whole cigarette smoke.

Previous investigations on the effects of cigarette smoke on cultured cells have used mainly smoke condensate dissolved in culture medium. A system has been designed which allows direct exposure of cells to fresh cigarette smoke, without an intervening layer of growth medium between the cells and the smoke. Preliminary results have been obtained which demonstrate the viability of the system. V79 cells were cultured on porous membranes (Transwell; Costar). During smoke exposure only the lower surface of each Transwell is supplied with culture medium from the bottom of the culture chambers. In this way the cells had direct contact with the atmosphere at the upper surface and could be exposed directly to the test compound. The constructed exposure system consists of a smoke generator and an exposure unit containing six Transwells, the latter contained in an incubator. Cigarette smoke was generated using a standard 2 s, 35 ml puff once per min. The puff is diluted with conditioned air from the incubator and injected into the exposure unit. Following exposure of the cells to air only for 3 h there was no effect upon V79 cell viability. However, after exposure to smoke containing between 88 and 224 mg/m3 particulate matter, an inhibition of cell proliferation and induction of micronuclei was measured. When a Cambridge filter pad was placed between the cigarette and the cell exposure system to remove particulate matter cell proliferation was also reduced and an increased frequency of micronuclei above the control value was measured.

Stromelysin-3 (ST-3) mRNA expression in colorectal carcinomas. Localization and clinicopathologic correlations.

Stromelysin-3 (ST-3) mRNA expression was studied in 28 colorectal carcinomas and compared with that of adjacent nontumorous tissue. By Northern blot analysis, levels of ST-3 mRNA were significantly increased in the carcinomas compared with ST-3 expression was seen with degree of invasion, nodal or distant metastases, or histologic grade. In situ hybridization of nontumorous tissue showed no significant ST-3 expression. In tumor tissue, ST-3 mRNA was localized adjacent to colon carcinoma cells in irregular foci within the stoma. No significant difference in ST-3 expression was found between the center and periphery of the colon tumors. Most of the colon carcinomas (26 of 28) induced an expression of ST-3 in the directly adjacent stroma. No significant correlation between ST-3 mRNA expression and tumor stage and grade was seen. By Northern blot, we also saw expression of ST-3 in noncarcinomatous tissue, further supporting the concept that ST-3 expression is a tumor-induced but not a tumor-specific phenomenon.

Efficacy of 5'-nor-anhydrovinblastine (vinorelbine), against freshly explanted clonogenic human tumor cells in vitro.

Vinorelbine (5'-nor-anhydrovinblastine) is a semisynthetic vinca alkaloid currently undergoing extensive clinical evaluation. We have studied the antitumor effect of vinorelbine (final concentrations: 8.4-1000.0 ng/ml) against freshly explanted clonogenic cells from 102 human tumors using a capillary soft agar cloning system and have compared the compound's activity with vinblastine, vincristine, vindesine, paclitaxel, docetaxel, and other clinically used anticancer agents. Four specimens were excluded from further analyses (3 bacterial or fungal contamination, 1 benign histology). Fifty-one of the remaining 98 (52%) specimens had adequate colony formation in control capillaries. Vinorelbine showed concentration-dependent antitumor activity against a variety of solid tumors. At clinically relevant concentrations (0.1 x peak plasma concentrations in humans) vinorelbine inhibited 21 of 49 specimens (43%) and was as active as vinblastine, vincristine, vindesine, bleomycin, doxorubicin, 5-fluorouracil, mitomycin-C, cisplatin, methotrexate, and etoposide. However, paclitaxel (71% inhibition, p = 0.006) and docetaxel (78% inhibition, p = 0.002) were significantly more active than vinorelbine. Moreover, vinorelbine showed antitumor activity against several tumor types and in particular against breast cancer but also in non-small cell lung cancer. We conclude that vinorelbine has a wide spectrum of in vitro activity against freshly explanted human tumors and that the clinical activity of this compound against breast cancer and non-small cell lung cancer is reflected in vitro.