Macular pigmentation complicating irritant contact dermatitis and viral warts in Laugier-Hunziker syndrome.

Laugier-Hunziker syndrome (LHS) is a rare acquired disorder characterized by macu-lar pigmentation of the lips and oral mucosa, with frequent longitudinal melanonychia. Involvement of other areas, such as the genitalia and fingers, has rarely been described. LHS is a benign condition with no known systemic manifestations. We report the case of a woman who developed melanotic macules on her fingers and elbow 16 years after the onset of pigmentation of her lips. This unusual feature of LHS in our patient was associated with irritant contact dermatitis and viral warts. Only two cases of an association with an inflammatory dermatosis have been reported previously in the literature.

Does dermatoneuro syndrome have a viral aetiology?

Scleromyxoedema is a rare disease characterized by a generalized papular and sclerodermoid cutaneous eruption. It is associated with fibroblast proliferation and mucin deposition in the dermis. Most patients have a monoclonal gammopathy, defined by the presence of IgG. Treatment of scleromyxoedema is challenging, but there is mounting evidence to support the use of intravenous immunoglobulin (IVIg). Individual reports of systemic complications have been described. Dermatoneuro syndrome (DNS) is a rare but sometimes fatal manifestation, which consists of a triad of fever, coma and seizures preceded by a flu-like illness. We describe a patient with scleromyxoedema who developed DNS. Our case highlights interesting findings suggesting that DNS may have a viral aetiology. In addition, this case demonstrates a favourable response of the cutaneous features of scleromyxoedema to IVIg.

The microbial growth potential of antiscalants used in seawater desalination.

20 years since the first report on the biofouling potential of chemicals used for scale control, still, antiscalants with high bacterial growth potential are used in practice. Evaluating the bacterial growth potential of commercially available antiscalants is therefore essential for a rational selection of these chemicals. Previous antiscalant growth potential tests were conducted in drinking water or seawater inoculated with model bacterial species which do not represent natural bacterial communities. To reflect better on the conditions of desalination systems, we investigated the bacterial growth potential of eight different antiscalants in natural seawater and an autochthonous bacterial population as inoculum. The antiscalants differed strongly in their bacterial growth potential varying from ≤ 1 to 6 µg easily biodegradable C equivalents/mg antiscalant. The six phosphonate-based antiscalants investigated showed a broad range of growth potential, which depended on their chemical composition, whilst the biopolymer and the synthetic carboxylated polymers-based antiscalants showed limited or no significant bacterial growth. Moreover, nuclear magnetic resonance (NMR) scans enabled antiscalant fingerprinting, identifying components and contaminants, providing a rapid and sensitive characterization, and opening opportunities for rational selection of antiscalants for biofouling control.

In situ source levels of mulloway (Argyrosomus japonicus) calls.

Mulloway (Argyrosomus japonicus) in Mosman Bay, Western Australia produce three call categories associated with spawning behavior. The determination of call source levels and their contribution to overall recorded sound pressure levels is a significant step towards estimating numbers of calling fish within the detection range of a hydrophone. The source levels and ambient noise also provide significant information on the impacts anthropogenic activity may have on the detection of A. japonicus calls. An array of four hydrophones was deployed to record and locate individual fish from call arrival-time differences. Successive A. japonicus calls produced samples at various ranges between 1 and 100 m from one of the array hydrophones. The three-dimensional localization of calls, together with removal of ambient noise, allowed the determination of source levels for each call category using observed trends in propagation losses and interference. Mean source levels (at 1 m from the hydrophone) of the three call categories were calculated as 163 ± 16 dB re 1 µPa for Category 1 calls (short call of 2-5 pulses); 172 ± 4 dB re 1 µPa for Category 2 calls (long calls of 11-32 pulses); and 157 ± 5 dB re 1 µPa for Category 3 calls (series of successive calls of 1-4 pulses, increasing in call rate).

Seawater Reverse Osmosis Performance Decline Caused by Short-Term Elevated Feed Water Temperature.

The shortage of fresh water resources has made the desalination of seawater a widely adopted technology. Seawater reverse osmosis (SWRO) is the most commonly used method for desalination. The SWRO process is energy-intensive, and most of the energy in SWRO is spent on pressurizing the seawater to overcome the osmotic barrier for producing fresh water. The pressure needed depends on the salinity of the seawater, its temperature, and the membrane surface properties. Membrane compaction occurs in SWRO due to hydraulic pressure application for long-term operations and operating temperature fluctuations due to seasonal seawater changes. This study investigates the effects of short-term feed water temperature increase on the SWRO process in a full-scale pilot with pretreatment and a SWRO installation consisting of a pressure vessel which contains seven industrial-scale 8" diameter spiral wound membrane elements. A SWRO feed water temperature of 40 °C, even for a short period of 7 days, caused a permanent performance decline illustrated by a strong specific energy consumption increase of 7.5%. This study highlights the need for membrane manufacturer data that account for the water temperature effect on membrane performance over a broad temperature range. There is a need to develop new membranes that are more tolerant to temperature fluctuations.

A solid-state NMR and DFT study of compositional modulations in Al(x)Ga(1-x)As.

We have conducted (75)As and (69)Ga Nuclear Magnetic Resonance (NMR) experiments to investigate order/disorder in Al(x)Ga(1-x)As lift-off films with x∼ 0.297 and 0.489. We were able to identify all possible As(Al(n)Ga(4-n)) sites with n = 0-4 coordinations in (75)As NMR spectra using spin-echo experiments at 18.8 Tesla. This was achieved by employing high rf field strengths using a small solenoid coil and an NMR probe specifically designed for this purpose. Spectral deconvolution, using an evolutionary algorithm, complies with the absence of long-range order if a CuAu based order parameter is imposed. An unconstrained fit shows a deviation of the statistics imposed by this type of ordering. The occupational disorder in the Ga and Al positions is reflected in a distribution of the Electric Field Gradients (EFGs) experienced at the different arsenic sites. We established that this can be modelled by summing the effects of the first coordination sphere and a Czjzek type distribution resulting from the compositional variation in the Al/Ga sub-lattice in the higher coordination spheres. (69)Ga 3QMAS and nutation data exclude the presence of highly symmetric sites and also show a distribution in EFG. The experimentally obtained quadrupolar interactions are in good agreement with calculations based on Density Functional Theory (DFT). Using additivity of EFG tensors arising from distant charge perturbations, we could use DFT to model the EFG distributions of the n = 0-4 sites, reproducing the Czjzek and extended Czjzek distributions that were found experimentally. On the basis of these calculations we conclude that the (75)As quadrupolar interaction is sensitive to compositional modulations up to the 7th coordination shell in these systems.

Removal of Common Bile Ducts Stones via Percutaneous Access with a Flexible Ureteroscope and Laser Assistance.

Two patients are described with large stones in the common bile duct. Standard ERCP was not possible. Both patients were successfully treated with percutaneous access and use of the ureteroscope with the holmium laser.

IN VITRO TRANSPLANTATION OF GENETICALLY MODIFIED CELLS TO THE TENDON SURFACE.

The objective of this paper was to study in vitro transfection of tendon cells and adherence of transfected cells to different tendon surfaces. Achilles tendon fibroblasts from 2-month-old New Zealand white rabbits were cultured to confluence, after which the cells were transfected by an adenovirus carrying either the ß-galactosidase reporter gene or the green fluorescent protein (GFP) gene at multiplicities of infection (MOIs) of 50, 100, or 500. Two days later, the cells were transplanted onto the surfaces of rabbit Achilles, peroneus brevis, flexor profundus, and extensor longus tendons. The tendons were assessed by X-gal staining after 9 days, and by GFP fluorescence at 7, 14, and 21 days. Twenty percent to 50% of the treated cells stained for ß-galactosidase at an MOI of 500. The GFP-labeled cells showed nearly 100% fluorescence at an MOI of 50. No positive cells were visible in the control group. The ß-galactosidase and GFP-expressing cells remained viable for as long as 3 weeks. It is possible to introduce foreign genes into rabbit tendon cells, transplant the cells onto tendon surfaces, and maintain viability of the cell/tendon construct for several weeks.

Secondary acute lymphoblastic leukemia is a distinct clinical entity with prognostic significance.

The effect of prior malignancy on the risk of developing, and prognosis of, acute lymphoblastic leukemia (ALL) is unknown. This observational study utilized the California Cancer Registry to estimate the risk of developing ALL after a prior malignancy using standardized incidence ratios (SIRs, 95% confidence intervals). ALL occurring after a malignancy with an SIR>1 (increased-risk (IR) malignancies) was considered secondary ALL (s-ALL). Adjusted hazard ratios (aHRs, 95% confidence intervals) compared the effect of s-ALL with de novo ALL on overall survival. A total of 14 481 patients with ALL were identified (1988-2012) and 382 (3%) had a known prior malignancy. Any prior malignancy predisposed patients to developing ALL: SIR 1.62 (1.45-1.79). Hematologic malignancies (SIR 5.57, 4.38-6.98) and IR-solid tumors (SIR 2.11, 1.73-2.54) increased the risk of developing ALL. s-ALL increased the risk of death compared with de novo ALL (aHR 1.38 (1.16-1.63)) and this effect was more pronounced among younger patients (age<40 years: aHR 4.80 (3.15-7.30); age⩾40 years: aHR 1.40 (1.16-1.69)) (interaction P<0.001). This population-based study demonstrates that s-ALL is a distinct entity that occurs after specific malignancies and carries a poor prognosis compared with de novo ALL, particularly among patients <40 years of age.

Genesis of clone size heterogeneity in megakaryocytic and other hemopoietic colonies: the stochastic model revisited.

OBJECTIVE: We previously showed that the distributions of the numbers of doublings (NbD) undergone by individual megakaryocyte progenitors before commitment to polyploidization are markedly skewed and can consistently be fitted to straight lines when plotted on semilogarithmic coordinates. The slope of such lines, which yields the probability of polyploidization per doubling, is made less steep by stimulators of megakaryocyte colony formation and is less steep in mixed erythroid-megakaryocyte than in pure megakaryocyte colonies. Therefore, megakaryocytopoiesis provides a unique model for the study of clonal heterogeneity in a hemopoietic lineage, which is the subject of this review. DATA SOURCES: Articles relevant to the interpretation of these data were selected from the authors' and public databases. DATA SYNTHESIS: Exponential NbD distributions were first explained by postulating that following the assembly of thrombopoiesis-specific regulators, megakaryocyte progenitors require only a single random event to arrest proliferation and commit to polyploidization. However, this stochastic model was refuted by data indicating that intrinsic properties of individual progenitors affect the NbD they achieve. We suggest that the unequal repartition of critical compounds (including receptors, signaling molecules, and gene regulators) inherent in the stem cell-progenitor transition causes a heritable heterogeneity in megakaryocyte progenitor responsiveness to polyploidization inducers. This model would be compatible with 1) the evidence for intraclonal synchronization in megakaryocyte and other hemopoietic clones generated by committed progenitors; 2) the low probability of polyploidization of the relatively insensitive bipotent megakaryocyte progenitors; and 3) the thesis that stimulators act in part by recruiting megakaryocyte progenitor cells endowed with lesser responsiveness to polyploidization inducers and higher proliferative potential. CONCLUSION: The responsiveness of individual megakaryocyte progenitors to polyploidization inducers may be a major determinant of the exponential shape of NbD distributions.

Abnormal splenic megakaryopoiesis in MPSV-induced myeloproliferative disease.

The myeloproliferative sarcoma virus (MPSV) induces a murine myeloproliferative syndrome characterized by an erythromyelemia, an anemia, a thrombocytopenia associated with a myeloproliferation in the spleen and a splenic and medullar fibrosis. We have used the in-vitro plasma clot technique to measure megakaryocytic precursors in the spleen and bone-marrow of MPSV-infected mice. We report that megakaryocytic colonies are increased, in number (X75), in concentration (X9) and in size, in the spleen but not in the bone-marrow of neoplastic mice. Furthermore, these splenic precursors are hypersensitive to growth factors present in the anemic mouse serum used in the culture system. These data show that the thrombocytopenia observed in the MPSV-induced neoplasia does not result from a lack of megakaryocyte precursors, but rather from an excess of megakaryocyte destruction. This ineffective splenic megakaryopoiesis associated with the presence of a massive splenic fibrosis make the MPS-induced neoplasia a suitable model for studying the perturbation of megakaryopoiesis in myeloproliferative syndrome associated with fibrosis.

Myeloperoxidase and elastase as markers of leukocyte activation during cardiopulmonary bypass in humans.

To assess leukocyte activation during cardiopulmonary bypass, we measured white blood cell and neutrophil counts and lysosomal enzyme release, especially myeloperoxidase and elastase, throughout the operation and for 5 days postoperatively. A newly developed double antibody radioimmunoassay of myeloperoxidase and an enzyme-linked immunosorbent assay for detection of the polymorphonuclear elastase-alpha 1-proteinase inhibitor complex were used to determine their plasma levels in 15 patients undergoing elective aorta-coronary bypass grafting. Preoperatively white blood cell counts and plasmatic levels of myeloperoxidase and elastase-alpha 1-proteinase inhibitor were normal. Because no correlation has yet been established between levels of myeloperoxidase and elastase-alpha 1-proteinase inhibitor, the aim of this prospective study was to evaluate the use of these enzyme levels as markers for leukocyte activation in vivo. We addressed the clinical situation of cardiopulmonary bypass because it offered the possibility of monitoring the comparative evolution of blood levels of these enzymes in parallel to white blood cell counts through well-defined steps corresponding to known events. We document the advantages of myeloperoxidase blood levels over elastase measurement as reflecting more rapidly the in vivo activation of leukocytes. The time course kinetics of these three measurements were not parallel. White blood cell counts remained stable at the beginning of bypass, whereas myeloperoxidase levels increased sharply and continuously as soon as bypass was instituted until the end of bypass. Elastase levels also increased, but later than myeloperoxidase, beginning when the patients was rewarmed. High elastase plasma levels persisted later than myeloperoxidase after bypass, in parallel with white blood cell counts. It thus clearly appears that changes in myeloperoxidase levels more rapidly reflect the activation state of leukocytes induced by cardiopulmonary bypass and surgery, whereas peak levels of elastase were delayed and parallel to white blood cell counts. From this model, in which the evolution of leukocyte numbers could be followed in relation with known steps of stimulation, it appears that myeloperoxidase is a sensitive marker for monitoring in vivo activation of white blood cells.

Corrosion analysis of NiCu and PdCo thermal seed alloys used as interstitial hyperthermia implants.

Ferromagnetic materials with low Curie temperatures are being investigated for use as interstitial implants for fractionated hyperthermia treatment of prostatic disease. Previous investigations of the system have utilized alloys, such as NiCu, with inadequate corrosion resistance, requiring the use of catheters for removal of the implants following treatment or inert surface coatings which may interfere with thermal characteristics of the implants. We are evaluating a palladium-cobalt (PdCo) binary alloy which is very similar to high palladium alloys used in dentistry. Electrochemical corrosion tests and immersion tests at 37 degrees C for both NiCu and PdCo alloy samples in mammalian Ringer's solution were performed. Long-term corrosion rates are 5.8 x 10(-5) microm per year (NiCu) and 7.7 x 10(-8) microm per year (PdCo) from average immersion test results, indicating higher corrosion resistance of PdCo (P < 0.02); immersion corrosion rates were much lower than initial corrosion rates found electrochemically. Both alloys had significantly lower corrosion rates than standard surgical implant rates of 0.04 microm per year (P < 0.001 for both alloys). Scanning electron microscopy illustrates changes in the NiCu alloy surface due to pitting corrosion; no difference is observed for PdCo. The data indicate that the PdCo alloy may be suitable as a long-term implant for use in fractionated hyperthermia.

Circadian and seasonal variations of hematopoiesis in cord blood.

Cord blood hematopoietic progenitors undergo circadian and seasonal variations. The lowest values are obtained between 4:00 and 12:00, as well as between May and August. This represents the first observation of such rhythms before birth.

A four-parameter index of marrow dysplasia has predictive value for survival in myelodysplastic syndromes.

Marrow dysplasia is a major characteristic of patients with myelodysplastic syndrome (MDS), along with marrow blastosis, cytopenia and cytogenetic anomalies. However, the impact of the degree of marrow dysplasia on survival has not been fully assessed. In this retrospective analysis of 111 patients selected according to the IPSS criteria of MDS diagnosis, the presence or absence of 21 dysplasia characteristics recognizable in bone marrow smears stained by the May-Grünwald-Giemsa method was correlated with patient survival. Using Cox proportional hazards regression analysis, megaloblastosis (MEGALO), neutrophil agranularity (AGRAN) and hypogranularity (HYPOGRAN) were highly significant predictors (p < 0.005), and Pelger-Huët anomaly (PELGHUET) a significant predictor (p = 0.05), of patient survival. The regression analysis yielded a dysplasia-based risk index (DI) where DI = 1.26 MEGALO + 0.82 AGRAN - 1.08 HYPOGRAN + 0.45 PELGHUET. The two subgroups of 60 and 47 patients with DI < or = 0 and > 0 showed highly significant differences in median survivals (2.6 vs 1.1 yrs; p <0.0001). Multivariate analysis further showed that DI offered additional predictive power that was independent of that provided by the IPSS (p=0.002 and 0.001 respectively). Analysis of survival curves stratified for IPSS and DI showed that the additional predictive power offered by inclusion of the DI essentially concerned the IPSS low/INT-1 risk categories. Further stratification for age did not improve survival prediction. The data indicate that a set of 4 dysplasia parameters can offer some prediction for survival of MDS patients in addition to that provided by the IPSS. Further multicenter studies should aim at including some form of evaluation of the degree of dysplasia in prognostic systems.

HSP 70 induction and thermotolerance following interstitial hyperthermia in the dunning R3327 tumor in vivo.

We investigated the use of an interstitial temperature self-regulating implant for fractionated hyperthermia delivery for treatment of prostatic disease. Nonuniform heating, lower temperatures between the implants, and lingering thermotolerance for additional hyperthermia treatments are concerns associated with the technique. Thermotolerance of the Dunning R3327 prostate adenocarcinoma to a 1 hour interstitial heating of 42-43°C has been estimated using inducible heat shock protein (HSP) 72 as an assay. The duration of thermotolerance in a nonuniformly heated tumor is necessary for optimization of multiple-treatment planning. HSP 72 expression is increased between 8 and 16 hours posttreatment. Growth curves for conditioned (treated once at 42-43°C minimum) tumors retreated at a minimum temperature of 45°C after 10 hours recovery (where elevated HSP 72 expression is evident) were compared with those retreated after 48 hours recovery (with normal HSP 72 expression) and with conditioned controls; both retreatment groups differed from controls (p < 0.0001). Growth curves for tumors with elevated HSP 72 expression after 10 hours differed from those retreated after 48 hours (p ≤ 0.0202). The results indicate that in vivo measurement of HSP 72 expression in the Dunning tumor is an adequate indicator of thermotolerance for optimal sequencing of hyperthermia fractions and that sufficiently high thermal doses are effective against thermotolerant cell populations.

Evaluation of inductively heated ferromagnetic alloy implants for therapeutic interstitial hyperthermia.

Ferromagnetic alloys heated by magnetic induction have been investigated as interstitial hyperthermia delivery implants for over a decade, utilizing low Curie temperatures to provide thermal self-regulation. The minimally invasive method is attractive for fractionated thermal treatment of tumors which are not easily heated by focused microwave or ultrasound techniques. Past analyses of ferromagnetic seeds by other authors depict poor experimental correlation with theoretical heating predictions. Improvements in computer hardware and commercially available finite element analysis software have simplified the analysis of inductively heated thermal seeds considerably. This manuscript examines end effects of finite length implants and nonlinear magnetic material properties to account for previous inconsistencies. Two alloys, Ni-28 wt% Cu (NiCu) and Pd-6.15 wt% Co (PdCo), were used for comparison of theoretical and experimental calorimetric results. Length to diameter (L/d) ratios of over 20 for cylindrical seeds are necessary for minimization of end effects. Magnetic properties tested for alloys of NiCu and PdCo illustrate considerable nonlinearity of these materials in field strength ranges used for induction heating. Field strength dependent magnetic permeabilities and calorimetric data illustrate that more detailed material information must be included to accurately estimate induction power loss for these implants.

Thermal ablation of canine prostate using interstitial temperature self-regulating seeds: new treatment for prostate cancer.

An interstitial temperature self-regulating implantable thermal seed for ablation of the prostate was investigated for the treatment of cancer. The technique is analogous to brachytherapy implants with three important advantages: highly localized temperatures may reduce complications, the thermal seed can be activated for retreatment at any point in time, and the seeds pose no radiation hazard to the clinical staff. Thermal seeds were implanted in the left lobe of the prostates in four dogs; the right lobe was a control to evaluate undesired heating outside the seed array. Linear-array thermometry probes were placed in both lobes, and the induction field for heating the implants was activated for 1 hour. After treatment, biopsies were taken from both lobes at 4-hour intervals up to 28 hours to evaluate thermal damage and thermotolerance as measured by expression of heat shock protein (hsp) 70. Only 5 minutes was required to heat the left lobe to 45 degrees to 55 degrees C. The maximum and minimum cumulative equivalent minutes at 43 degrees C (CEM43) thermal doses in the treated lobe were 174 and 4.4 hours, respectively; less than a 1-minute CEM43 was observed in the control lobe. Elevated hsp70 expression was detected in tissue of the treated lobe between 12 and 24 hours after treatment; minimal increases occurred in the control lobe. The thermal seed system was effective at heating the prostatic volume without damage to normal tissues outside the implant array, and subsequent treatments were simplified in comparison with other hyperthermia devices. Expression of hsp70 implies that retreatment of the prostate at intervals as short as 48 to 72 hours may avoid thermotolerance making weekly treatment an appropriate regimen.

Influence of laminin or fibroblasts upon colony formation in the mouse by B16 melanoma cell spheroids: a morphometric analysis.

By microscopical observation and using an original morphometric method, we analyzed on histological sections the rate of lung colony formation after the intravenous injection into the mouse of B16 melanoma cells previously cultivated in vitro as aggregates. After the injection of B16 pure spheroids, superficial lung colonies were more numerous than internal lung colonies. After the injection of mixed spheroids (B16 + 3T3 fibroblasts), the size of colony sections was increased. Addition of laminin to pure or mixed spheroids decreased the size of colony sections but increased the number of internal lung colonies.

[Treatment results and the prognosis in patients with localization of non-Hodgkins-lymphoma in the central nervous system]. / Behandelresultaten en prognose bij patiënten met centralezenuwstelsellokalisaties van het non-Hodgkin-lymfoom.

OBJECTIVE: A description of clinical features and treatment results in patients with a central nervous system (CNS) localization of systemic non-Hodgkin's lymphoma (NHL). DESIGN: Retrospective. SETTING: Department of Neuro-oncology and Haematology, Daniel den Hoed Cancer Centre, Rotterdam, the Netherlands. METHODS: All patients with NHL (but not primary CNS lymphoma) treated in the period January 1st, 1990-December 31st, 1996 at the department of neuro-oncology were reviewed for presence of CNS localizations. Clinical characteristics like malignancy grade, disease stage, presence of extranodal localizations, B-symptoms, serum LDH, neurological signs and symptoms, results of ancillary investigations, treatment and response were recorded. RESULTS: In this period 25 patients were diagnosed with leptomeningeal lymphoma, 2 with an intracerebral lymphoma, and 7 with both. In almost all patients the CNS localization developed during systemic progression of the NHL. Most patients presented with a radicular syndrome, cranial nerve deficits, headache or encephalopathy. More than 80% of the patients showed clinical improvement after treatment with intrathecal chemotherapy, radiation therapy or a combination of both. The median survival was three and a half months, six month survival was 32%. Progression of systemic disease was the most frequent cause of death. CONCLUSION: In most patients good palliation of neurological signs and symptoms could be obtained with intrathecal chemotherapy and radiation therapy. Survival in these patients was limited, however, in part because of the frequent concurrent progression of systemic disease. Patients with CNS localizations with chemotherapeutic treatment possibilities with a realistic chance of cure or longterm survival should be treated accordingly. Otherwise, treatment should consist of intrathecal chemotherapy or radiation therapy of involved areas only.