Lumbar Drain Use during Middle Fossa Approaches for Nonneoplastic Pathology of the Skull Base.

Introduction The middle fossa craniotomy (MFCs) is commonly utilized for spontaneous cerebrospinal fluid (CSF) leaks, encephaloceles, and superior semicircular canal dehiscence (SSCD). This study compares postoperative outcomes of MFCs with and without LD use. Methods A retrospective cohort study of adults over the age of 18 years presenting for the repair of nonneoplastic CSF leak, encephalocele, or SSCD via MFC from 2009 to 2021 was conducted. The main exposure of interest was the placement of an LD. The primary outcome was the presence of postoperative complications (acute/delayed neurologic deficit, meningitis, intracranial hemorrhage, and stroke). Secondary outcomes included operating room (OR) time, length of stay, recurrence, and need for reoperation. Results In total, 172 patients were included, 96 of whom received an LD and 76 who did not. Patients not receiving an LD were more likely to receive intraoperative mannitol ( n = 24, 31.6% vs. n = 16, 16.7%, p = 0.02). On univariate logistic regression, LD placement did not influence overall postoperative complications (OR: 0.38, 95% confidence interval [CI]: 0.05-2.02, p = 0.28), CSF leak recurrence (OR: 0.75, 95% CI: 0.25-2.29, p = 0.61), or need for reoperation (OR: 1.47, 95% CI: 0.48-4.96, p = 0.51). While OR time was shorter for patients not receiving LD (349 ± 71 vs. 372 ± 85 minutes), this difference was not statistically significant ( p = 0.07). Conclusion No difference in postoperative outcomes was observed in patients who had an intraoperative LD placed compared to those without LD. Operative times were increased in the LD cohort, but this difference was not statistically significant. Given the similar outcomes, we conclude that LD is not necessary to facilitate safe MCF for nonneoplastic skull base pathologies.

Techniques to Reduce the Rate of Infection in Surgeries for Cerebrospinal Fluid Shunting in Adults.

OBJECTIVE: Cerebrospinal fluid shunt placement is associated with high rates of infection. Multiple standardized protocols, particularly in pediatric populations, have been proposed to mitigate this infection rate. We sought to determine the effectiveness of a standardized shunt infection protocol in a large adult population. METHODS: A retrospective cohort study of adults presenting for primary cerebrospinal fluid shunt placement from 2012 to 2022. The primary outcome of interest was shunt infection. The primary exposure of interest was implementation of the shunt protocol (began October 2015). Secondary exposures of interest included use and type of perioperative antibiotics and total operating room time. RESULTS: In total, 820 patients were included, 140 before protocol implementation and 680 after protocol implementation. The overall number of infections over the study period was 15 (1.8% infection rate), with 8 infections preprotocol (5.7%) and 7 infections during the protocol period (1.0%). The infection protocol was associated with a decreased infection rate (odds rato [OR] 0.18, 95% confidence interval [CI] 0.05-0.58, P = 0.002). Total operating room time (OR 1.38 per 30-minute increase, 95% CI 1.05-1.81, P = 0.021) was associated with increased infection rate. Patients who received antibiotics with primarily gram-positive coverage (cefazolin or equivalent) did not have significantly different odds of shunt infection as patients who received broad-spectrum coverage (OR 2.10, 95% CI 0.56-7.88, P = 0.274). CONCLUSIONS: The implementation of an evidence-based perioperative shunt infection protocol is an effective method to decrease shunt infections. Broad-spectrum perioperative antibiotics may not have greater efficacy than gram-positive only coverage, but more research is required.

The role of traditional social determinants of health in referral patterns, timing of surgery, and Chiari Health Index for Pediatrics-determined quality of life in children with symptomatic Chiari type I malformation.

OBJECTIVE: Understanding the impact of the social determinants of health on the utilization of healthcare resources is an important step in eliminating inequalities. The goal of this study was to determine the role of social determinants of health in referral patterns, timing of consultation/intervention, and quality of life in children with Chiari malformation type I (CM-I). METHODS: A retrospective study was conducted of children aged 0 to 18 years who underwent surgical treatment for CM-I at a single pediatric facility from 2015 to 2019. The variables included demographic and socioeconomic characteristics, referral patterns, timing, and quality of life data based on the Chiari Health Index for Pediatrics (CHIP). RESULTS: The cohort consisted of 103 surgically treated CM-I patients. No differences were seen in race, sex, insurance, or household income when evaluating referral source (community, specialist, or emergency department) or when comparing patients with incidental versus symptomatic findings. In the evaluation of timing from initial evaluation to surgery, no statistical differences were seen between racial, sex, insurance status, or income groups. Children from households of lower median family income were significantly more likely to report pain at the time of consultation (pain group median [interquartile range] $46,660 [$41,004-$50,367] vs nonpain group $53,604 [$41,427-$59,828], p = 0.004). Those in the lower-income group also reported lower CHIP scores corresponding to increased symptomatology in the nonpain physical symptoms (p = 0.004) and psychosocial domains (p = 0.018). CONCLUSIONS: There was no evidence of a difference in referral patterns or a delay in time from clinic presentation to surgery based on the traditional social determinants of health categories. Children from households in the lower-income group were associated with increased severity of pain and nonpain symptoms.

A method to quantify crystallinity in amorphous metal alloys: A differential scanning calorimetry study.

We developed and describe a differential scanning calorimetry method for calculating the initial crystallinity, change of crystallinity and crystallinity percentage of amorphous metal alloys as a function of temperature. Using thermodynamic enthalpies of amorphous, crystalline and partially devitrified specimens, our methodology is capable of determining crystallinity percentages as low as a few percent. Moreover, the linear relationship between the set (pre-determined) and calculated crystallinities of experimental samples indicates that there is no need to prepare calibration samples before measuring the crystallinity percentage of target samples. This technique also eliminates the need for expensive in situ accessories, such as those required in electron microscopy. Thus, the technique is highly relevant as a primary technique for characterization of devitrification behavior in amorphous materials.

Técnica de microinjerto Meek modificada para la cobertura de grandes quemados / Modified Meek micrograft technique for coverage of large burns

INTRODUCCIÓN Y OBJETIVO: Ante un quemado de gran extensión (más del 30%) con zonas donantes limitadas, la cobertura cutánea con la técnica de microexpansión modificada Meek es eficiente y eficaz. El objetivo de este trabajo es describir dicha técnica, revisar las publicaciones al respecto y destacar sus ventajas sobre la técnica de mallado tradicional de injertos. MATERIAL Y MÉTODO: Hacemos una puesta al día de los hechos históricos, descripción de la técnica quirúrgica de la microexpansión modificada Meek y revisión de la literatura con busquedas bibiografícas en inglés y español entre 1958 y 2019 empleando como palabras claves: (mesh) 'micrograft', 'micrograft tenchnique', Meek ', 'Meek technique, 'major burn treatment', y 'mesh skin graft'. Hacemos también una comparación de resultados con nuestra experiencia local. RESULTADOS: En nuestra experiencia, entre 2008 y 2010 tratamos 4 pacientes con quemaduras extensas y zonas dadoras limitadas, todos producto de accidentes laborales, con edad media de 47 años y promedio de superficie corporal quemada total (SCQT) del 63%. Empleamos microexpansión en tasa de 1:6 logrando cierre definitivo de las lesiones a las 4 semanas. Al comparar con la literatura publicada, observamos beneficios como disminución de estancia hospitalaria, número de procedimientos quirúrgicos realizados y baja morbimortalidad. CONCLUSIONES: La microexpansión modificada Meek en la cobertura cutánea de pacientes con quemaduras extensas y zonas dadoras de injertos limitadas constituye una herramienta eficiente y eficaz

BACKGROUND AND OBJECTIVE: In patients with extensive burns (greater tan 30%) and limited donor areas, skin coverage with the Meek modified microexpansión technique offers to be an efficient and effective technique. The objetive of this paper is to describe the technique, review the publications and highliht its advantages over the traditional grafting mesh technique. METHODS: We update the historical facts, description of the surgical technique of the Meek modified microexpansion and review the English and Spanish literature betwen 1958 and 2019 serarching with keywords: (mesh) 'micrograft', 'micrograft tenchnique', Meek ', 'Meek technique, 'major burn treatment', y 'mesh skin graft'. Finally we compare results with our local experience. RESULTS: In our experience, between 2008-2010, 4 patients with extensive burns and limited donor areas were treated with the Meek modified microexpansion technique for skin coverage, with an average age of 47 years and average of total burned body surface (SCQT) of 63%. Microexpansion was used at a rate of 1: 6, and definitive closure of his injuries was achieve at 4 weeks. When comparing with the published literature, benefits are shown with the decrease in hospital stay, number of surgical procedures and low morbidity and mortality. CONCLUSIONS: The use of the Meek modified microexpansion technique in the skin coverage of patients with extensive burns and limited graft donor areas is an efficient and effective method, compared to the dermoepidermic graft mesh technique

Characterizing the Performance of Pipe Bombs.

Pipe bombs of steel or PVC fragment in reproducible patterns when similarly configured. The power of the explosion correlates with number, mass, and size of the fragments recovered, where a large number of small, low-mass fragments indicate a high-power event and vice versa. In discussing performance, describing pipe fragmentation pattern by fragment weight distribution mapping (FWDM) or fragment surface area distribution mapping (FSADM) was useful. When fillers detonated, detonation velocities of ~4.4 mm/µs were measured. In such cases, side walls of the pipe were thrown first; the average fragment velocity was ~1000 km/s. In deflagrations, the end cap was first thrown; fragment velocities were only ~240 km/s. Blast overpressures varied; at 10 feet, 2 × 12 inch steel pipes containing ~550 g of detonable mixture produced overpressures of 5-6 psi; similar nondetonating pipes produced less than 2 psi. Maximum fragment throw distances were 250-300 m, with an average of ~100 m.

Participation and health care provision of statutory skin cancer screening in Germany - a secondary data analysis.

BACKGROUND: In Germany, skin cancer screening was introduced nationwide in July 2008. From the age of 35 years, members of the statutory health insurance are eligible for screening every 2 years. OBJECTIVE: The aim of this study is to calculate the participation rates and the proportions of health care providers of statutory skin cancer screening in Germany on a population-based level. METHODS: Data were provided by a nationwide German statutory health insurance, approximately 6.1 million members, covering the years 2008/2009. Participation rates were calculated per yearly quarter and were adjusted for age, gender and federal state. RESULTS: Approximately 920,000 insurants were screened from the third quarter of 2008 until the last quarter of 2009. Mean participation rate of skin cancer screening was 30.8%. Women had higher participation rates (31.9%) than men (29.7%). After adjusting for gender and federal state, high rates for pensioners at the age of 65-74 were confirmed at 39.4% on average for all yearly quarters. One of the highest gender- and age-adjusted rates was observed in the state of Schleswig-Holstein, where a population based pilot project had been implemented before the start of the nationwide screening programme. In general, without taking into account Berlin, former East Germany had a much lower gender- and age-adjusted participation rate (23.9%) than West Germany (33.3%). At the first quarter after implementation of screening, 58.5% of the screenings were provided by dermatologists and 41.5% by general practitioners. CONCLUSION: Participation rates and health care providers of skin cancer screening can be calculated from secondary data and contribute to identify group- and region-specific participation patterns in order to improve early detection of skin cancer.

Assessment of medical waste management at a primary health-care center in São Paulo, Brazil.

According to the Brazilian law, implementation of a Medical Waste Management Plan (MWMP) in health-care units is mandatory, but as far as we know evaluation of such implementation has not taken place yet. The purpose of the present study is to evaluate the improvements deriving from the implementation of a MWMP in a Primary Health-care Center (PHC) located in the city of São Paulo, Brazil. The method proposed for evaluation compares the first situation prevailing at this PHC with the situation 1 year after implementation of the MWMP, thus allowing verification of the evolution of the PHC performance. For prior and post-diagnosis, the method was based on: (1) application of a tool (check list) which considered all legal requirements in force; (2) quantification of solid waste subdivided into three categories: infectious waste and sharp devices, recyclable materials and non-recyclable waste; and (3) identification of non-conformity practices. Lack of knowledge on the pertinent legislation by health workers has contributed to non-conformity instances. The legal requirements in force in Brazil today gave origin to a tool (check list) which was utilized in the management of medical waste at the health-care unit studied. This tool resulted into an adequate and simple instrument, required a low investment, allowed collecting data to feed indicators and also conquered the participation of the unit whole staff. Several non-conformities identified in the first diagnosis could be corrected by the instrument utilized. Total waste generation increased 9.8%, but it was possible to reduce the volume of non-recyclable materials (11%) and increase the volume of recyclable materials (4%). It was also possible to segregate organic waste (7%), which was forwarded for production of compost. The rate of infectious waste generation in critical areas decreased from 0.021 to 0.018 kg/procedure. Many improvements have been observed, and now the PHC complies with most of legal requirements, offers periodic training and better biosafety conditions to workers, has reduced the volume of waste sent to sanitary landfills, and has introduced indicators for monitoring its own performance. This evaluation method might subsidize the creation and evaluation of medical waste management plans in similar heath institutions.

Is there an association between hospital accreditation and patient satisfaction with hospital care? A survey of 37,000 patients treated by 73 hospitals.

OBJECTIVE: In many countries hospitals are undergoing accreditation as mandatory or voluntary measures. It is believed that accreditation positively influence quality of care and patient satisfaction. This survey aims at assessing the relationship between patient satisfaction and accreditation status. DESIGN: Between January and May 2007, 4 weeks after their discharge, 78 508 patients from 328 departments in 73 hospitals received a validated questionnaire. Data from 36 777 patients (response rate 55%) were available for analyses. MAIN OUTCOME MEASURES: Recommendation rate was used as primary endpoint, which was available from 35 945 patients. To address the clustering of patients within hospitals, we applied univariate and multivariable generalized estimating equations. As covariates we used 'gender' and 'age' at the patient level and the 'number of beds' and 'hospital teaching status' at the hospital level. RESULTS: Overall and not addressing the clustering, 66.3% of all the patients recommend their hospital to others. This recommendation, however, was not related to the accreditation status in the univariate analyses (odds ratio (OR) for accreditation ('yes') and recommendation ('yes') 0.99, 95% confidence interval (CI) 0.85-1.16, P= 0.92). This result was similar in the multivariable regression model adjusted for clustering (OR = 0.98, 95% CI 0.84-1.13, P= 0.74). CONCLUSIONS: Our results support the notion that accreditation is not linked to measurable better quality of care as perceived by the patient. Hospital accreditation may represent a step towards total quality management, but may not be a key factor to quality of care measured by the patient's willingness to recommend.

Segmental Mobility in the Non-crystalline Regions of Semicrystalline Polymers and its Implications on Melting.

Detailed knowledge on chain mobility in polymers is of fundamental interest in order to understand their mechanical properties. As a specific example, the melting behavior of semicrystalline polyethylene can be studied by thermal analysis and NMR spectroscopy. In ultra high molecular weight polyethylene (UHMW-PE) crystallised via different routes, i.e., directly during polymerisation, from solution, or from the melt, and melted under different protocols, different melting processes involving detachment of stems from the crystals and cluster melting can be distinguished. Melting by the consecutive detachment of chain stems from the crystal substrate ultimately results in a melt state where chain dynamics for entanglement formation are much more restricted.

Sanitation assessment of wastewater treated by stabilization ponds for potential reuse in agricultural irrigation sanitation assessment.

Wastewater reuse has become an important alternative to agricultural irrigation; on the other hand, it poses concern with regard to public health. Total coliform and Escherichia coli concentration, presence of helminth eggs and Salmonella, and physical-chemical parameters were evaluated in raw and treated wastewater. Chemical and biochemical oxygen demand removal efficiency was 74.6 and 77.9%, respectively. As for organic nitrogen, total phosphorus, and total suspended solids, total efficiency removal was 17.4, 12.5, and 32.9%, respectively. The average density of total coliforms and E. coli was 3.5 x 10(9) and 1.8 x 10(8) MPN/100 mL and 1.1 x 10(7) MPN/100 mL and 3.9 x 10(5) MPN/100 mL for raw and treated wastewater, respectively. Ascaris eggs were observed in 80.8% of the samples collected, and viable eggs in 42.3% of the samples. Salmonella was detected in 36.4% of the samples. The values observed in treated wastewater did not show the adequate bacteriological quality, as recommended by World Health Organization (Geneva, Switzerland). Therefore, additional measures should be taken to achieve an improved microbiological and parasitological quality.

Transarterial nephrectomy: the current status of experimental and clinical studies.

INTRODUCTION: Open nephrectomy is associated with significant morbidity. For several years, minimally invasive alternatives have been developed such as laparoscopic nephrectomy or transarterial renal ablation. This paper focuses on the different principles of vaso-occlusion and further improvements of the technique such as capillary chemoembolization in experimental as well as clinical studies. MATERIALS AND METHODS: Based on own in vitro studies, the principle of capillary embolization with occlusion of the entire arterial system up to the capillaries by a precipitating corn protein (Ethibloc) has been developed in animal studies (i.e., rat and canine kidney model). The precipitation speed of Ethibloc can be prolonged by 40% glucose per injection. The organ-ablative efficacy was evaluated in models of unilateral hypertension and chemically induced renal tumors (i.e., dimethyl-nitrosamine). Further studies using the model of unilateral transarterial implantation of Yoshida-sarcoma cells compared capillary chemoembolization using Ethibloc/mitomycin C (MMC) versus chemoperfusion and capillary embolization. Before starting clinical trials, the optimal mixture of Ethibloc and MMC was determined in vitro and in vivo. Prior to the vaso-occlusion, the volume of the arterial system of the kidney is determined by perfusion of the kidney with contrast-dye via a blocked balloon-catheter. Then 25% of the determined volume of 40% glucose is pre-injected followed by Ethibloc/MMC being injected with 1-cm(3) syringes. Once the capillary bed and tumor sinusoids are reached, the balloon catheter is emptied by postinjection of 40% glucose. RESULTS: Capillary embolization proved to be significantly superior to a central (i.e., ligation of renal artery) or peripheral type of occlusion resulting in complete coagulation necrosis of the normal rat and canine kidney with reduction of the elevated blood pressure, similar to nephrectomy in the model of renal hypertension. In the model of chemically induced renal tumors, complete necrosis of T2 stages could be achieved in 83% using Ethibloc compared to only 63% with Gelfoam particles, and 17% after ligation. In T3/T4 stages, the response rate was only 60% versus 0% after central and peripheral occlusion. In the highly aggressive Yoshida-sarcoma model, capillary chemoembolization yielded an 80% complete response rate compared to only 75% after capillary embolization and 70% after chemoperfusion. The optimal mixture of Ethibloc and MMC ranged between 1 and 2 mg of MMC to 1 cm(3) of Ethibloc, therefore for clinical trials 10 mg MMC was added to the 7.5 cm(3) syringe of Ethibloc. Clinical studies included 68 preoperatively as well as 62 palliatively embolized patients with renal cell carcinoma. The procedure was relatively well tolerated and usually associated with a mild postembolization syndrome. After an interval of up to 28 days, complete necrosis of the renal tumor could be achieved in tumors up to 9 cm in diameter. Hematuria ceased in all cases, and in selected cases long-lasting responses of very large tumors (i.e., vena cava involvement) could be achieved. DISCUSSION: Capillary chemoembolization represents an effective concept for ablation of malignant renal tumors. It offers control of tumor growth in case of temporary inoperability as well as cessation of hematuria in a palliative situation. Because of the local ablative efficiency, it may still represent a minimally invasive option in advanced stages of renal carcinoma (i.e., in combination with immunochemotherapy or targeted therapy).

N,N-Dialkylaminostyryl dyes: specific and highly fluorescent substrates of peroxidase and their application in histochemistry.

Fluorescent labeling of immuno-bound or endogenous peroxidase (PO) activity has been achieved to date by means of phenol derivatives with a low substitution degree. Here it is demonstrated that N,N-dialkylamino-styryl dyes can also act as fluorescent substrates of PO. They undergo enzymatically cross-linking reactions to surrounding cell constituents in an analogous manner thus permitting highly fluorescent and permanent labeling. This approach is narrowly related to the catalyzed reporter deposition (CARD) technique based on tyramine conjugates and the recently described catalytic cross-linking approach of hydroxystyryl derivatives. The substitution patterns for optimal cross-linking capability and the spectral properties of obtained specific reaction products were studied using an iterative semi-empirical approach. The best staining performance is achieved with N,N-dimethylaminoaryl derivatives. Their N,N-dialkyl homologues as well as the primary aryl amine pendants failed as PO substrates. Due to their basic character, novel substrates occasionally tend to unspecific interactions (staining nuclei, mast cells, or keratin). Centering this side specificity and repressing the staining capability of PO was achieved by chemical modification of the respective dye leading to new specific probes for keratin and cytoplasmatic RNA. In conclusion, catalytic cross-linking of heterocyclic 4-N,N-dimethylamino-styryl dyes represents a promising approach for the permanent fluorescent staining of PO in fixed cells and tissues, complementing the CARD technique. In contrast to CARD-related approaches, new substrates are characterized by a broad excitation and emission range of fluorescence and the outstanding spatial resolution of specific fluorescence signaling known so far from their 4-hydroxystyryl analogues. They currently represent the smallest fluorescent substrates of PO. Histochemical and immuno-histochemical applications share several outstanding features: High detection sensitivity, spatial resolution of fluorescence signaling, and photo stability. 4-N,N-dimethylamino-styryl substrates are compatible with their phenol and phenol-ester analogues. Their combination facilitates the trichromatic immuno-histochemical demonstration of three different targets simultaneously at one excitation wavelength in a conventional epi-fluorescence microscope.

Optimization of heterocyclic 4-hydroxystyryl derivatives for histological localization of endogenous and immunobound peroxidase activity.

Assisted by the development of light excitation and measuring techniques and the commercial availability of highly sensitive equipment, luminescent labels are sensitive detection tools for life sciences research. By contrast to a wide variety of well established chromogenic techniques, fluorescent labels for detecting peroxidase (PO) have been confined to only a few substrates. We describe here novel fluorescent substrates of PO derived from heterocyclic 4-hydroxy styrenes as useful tools for detecting endogenous and exogenous targets in fixed cells and tissues. Excellent localization, high staining sensitivity, outstanding photostability, and exceptionally low background staining were achieved by optimizing the substrate through chemical synthesis. Structure/staining behavior relationships are discussed. By contrast to tyramine-fluorochrome conjugates employed in the catalyzed reporter deposition (CARD) technique, reporting and anchoring functions are no longer separated. Consequently, enzymatic cross-linking of the substrate yields an altered fluorochrome with different properties. Spectral properties and anchoring capability are interdependent and influenced by environmental effects and pH. We screened overall staining capability of 4-hydroxy styryl derivatives using an iterative semi-empirical approach, and ascertained optimal substitution patterns for high PO staining specificity and high fluorescence response. Reliable staining performance was achieved with alkyl chains of short or medium length at the positively charged nitrogen, whereas introducing polar groups often impaired the staining specificity of PO. Catalytic cross-linking of heterocyclic 4-hydroxy-styryl derivatives is a promising approach for permanent fluorescent staining of PO in fixed cells and tissues, and complements the CARD technique. Histochemical and immunohistochemical applications are presented using conventional and confocal fluorescence microscopes with different excitation sources. Spectral properties of selected stains are discussed. Novel stains also are of potential interest as "reactive-tracers" for living cells under multi-photon laser excitation conditions, because they exhibit pronounced nonlinear optical properties.

[Differential indications for atypical neuroleptics: Amisulprid, Clozapin, Olanzapin, Quetiapin und Risperidon. Results of a pilot study of prescription habits in psychiatric clinical usage in the BRD]. / Differenzialindikation atypischer Neuroleptika: Amisulprid, Clozapin, Olanzapin, Quetiapin und Risperidon. Ergebnisse einer Pilotstudie zu Verordnungsgewohnheiten in psychiatrischen Versorgungskliniken der BRD.

With the introduction of atypical neuroleptics, the therapy of schizophrenia has been improved by a group of antipsychotic substances characterized by better tolerability concerning extrapyramidal side effects and higher efficiency against negative symptoms. However, these atypical antipsychotics are not a homogeneous class of drugs but rather represent a group of substances with very different neurobiologic, pharmacologic, and clinical features. This fact and the growing variety of available atypical neuroleptics illustrate the difficulty in choosing the "right" antipsychotic drug for each patient. The aim of this investigation was to evaluate preliminary empirical data for possible differential indication of atypical neuroleptics by a questionnaire-based survey of 192 physicians in ten psychiatric hospitals active in the biological psychiatry work group of the German Federal Directors' Conference.

Molecular approaches to brain tumour invasion.

In glioma cells, the stimulatory input of extracellular matrix components and an increased sensitivity to growth factors result in a high proliferative and migratory behaviour. Cell surface receptor interactions play pivotal roles in converging information about conditions in the environment immediately outside the cell. The transduced signal, in turn induces a response within the cell that provokes a specific behaviour. Cellular migration and cell proliferation are interwoven processes that share several common intracellular pathways. The major cross-links are the phosphoinositol phosphate regulating enzymes, PI-3 kinase and PTEN, the focal adhesion kinase (FAK) and the tumour suppressor p53. An understanding of the interaction between the molecular participants involved in migration and proliferation will promote the design of new treatments. A full understanding of the basis of the invasiveness of tumour cells remains elusive. Gene and protein expression are being studied, using modern techniques such as microarray analysis, SAGE and 2-D protein gels. Transient and permanent protein-protein interactions and recruitment of proteins to specialised cellular domains are equally important in regulating cellular invasion and presumably will attract more attention in future.

Dose-dependent effects of in vivo antithymocyte globulin during conditioning for allogeneic bone marrow transplantation from unrelated donors in patients with chronic phase CML.

We conducted a dose-escalation study with antithymocyte globulin (ATG) in patients undergoing unrelated donor bone marrow transplantation (URD-BMT). This study analyzes the results for 97 patients with chronic myelogenous leukemia (CML) in first chronic phase. Median age was 36 years (16-51). In all, 40 patients were transplanted within 2 years after diagnosis and 57 later during disease. ATG-S (Fresenius) 20-120 mg/kg body weight (b.w.) was given prior to transplantation. A total of 31 patients received less than 60 mg/kg b.w. and 66 patients received 60 mg/kg b.w. or more. All patients except one were grafted with bone marrow, and graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporin A and methotrexate. Graft failure did occur in one patient. Grade II-IV acute GVHD developed in 56.7% and extensive chronic GVHD in 11.3% of the patients. The relapse rate was 13.4%. With a median follow-up of 5.8 years (1.5-12.1), 5-year disease-free and overall survival for all patients were 56 and 66%, and for patients transplanted within 2 years of diagnosis it was 72 and 82%. A lower dose of ATG was a significant risk factor for poor outcome. In summary, URD-BMT remains an excellent treatment option for patients with early phase CML, if a sufficient amount of ATG is included in the preparative regimen.