Betaproteobacteria are a key component of surface water biofilters that maintain sustained manganese removal in response to fluctuations in influent water temperature.

The health risks associated with manganese (Mn) in drinking water, and an improved understanding of Mn accumulation within, and subsequent release from, distribution systems, have increased the need for robust, sustainable treatment options to minimize Mn concentrations in finished water. Biofiltration is an established and effective method to remove Mn in groundwater however, Mn removal in surface water biofilters is an emerging treatment process that has not been extensively studied. Seasonal variations in water temperature can present an operational challenge for surface water biofilters which may see reduced Mn removal under colder conditions. This study examined the microbiomes of surface water biofilters at three utilities (ACWD WTP, WTP B, and WTP D) which all experienced similar seasonal fluctuations in influent water temperature. High Mn removal was observed at the ACWD WTP for much of the year, but Mn removal decreased with a concurrent decrease in the influent water temperature (58% ± 22%). In contrast, both WTP B and WTP D achieved year-round Mn removal (84% ± 5% and 93% ± 8% respectively). Marker gene (16S rRNA) sequencing analysis of the biofilter microbiomes identified a high abundance of Betaproteobacteria in WTP B and WTP D (37% ± 12% and 21% ± 3% respectively), but a low abundance of Betaproteobacteria in the ACWD WTP (2% ± 2%). The microbiomes of new bench-scale biofilters, in operation at the ACWD WTP, were also investigated. The abundance of Betaproteobacteria was significantly greater (p < 0.05) after the biofilters had acclimated than before acclimation, and differential abundance analysis identified 6 genera within the Betaproteobacteria class were enriched in the acclimated microbiome. Additionally, the acclimated biofilters were able to maintain high Mn removal performance (87% ± 10%) when the influent water temperature decreased to 10 °C or less. Further analysis of previously published studies found the abundance of Betaproteobacteria was also significantly greater (p < 0.001) in biofilters with sustained Mn removal than in biofilters which did not treat for Mn as a contaminant, despite differences in design scale, source water, and media type. Microbiome network analysis identified multiple co-occurrence relationships between Betaproteobacteria and Mn oxidizing bacteria in the WTP B and WTP D biofilters, suggesting indirect contributions by Betaproteobacteria to biological Mn oxidation. These co-occurrence relationships were not present in the full-scale ACWD WTP microbiome. Whether the role of Betaproteobacteria in biological Mn oxidation is direct, indirect, or a combination of both, they are consistently present at a high abundance in both groundwater and surface water biofilters with sustained Mn removal, and their absence may contribute to the seasonal fluctuations in Mn removal observed at the ACWD WTP. This new insight to Betaproteobacteria and their role in Mn biofiltration could contribute to water innovation and design that would improve the reliability of Mn removal.

Biological and physico-chemical mechanisms accelerating the acclimation of Mn-removing biofilters.

This study investigated treatment strategies which accelerated the acclimation of new Mn-removing biofilters to help utilities respond to changing Mn regulations, such as the recent introduction of a health-based maximum acceptable concentration and a reduction in the aesthetic objective for Mn in drinking water by Health Canada. Bench-scale filters of either GAC or anthracite media were fed with applied water containing Mn (17-61 µg/L) from a full-scale plant over 294 days. Treatment strategies included the addition of H2O2 (1 mg/L) and/or an increase in pH from 6.8 to 7.5 through the addition of NaOH. The potential physico-chemical and biological mechanisms responsible for accelerated biofilter acclimation under the various redox conditions were investigated through thermodynamic modelling, to predict homogeneous Mn oxide formation, and 16S rRNA gene amplicon sequencing, to characterize the microbial community within the filters. GAC filters treated with NaOH, and both H2O2 and NaOH, were the first to acclimate (< 20 µg/L Mn in filter effluent) after 59 and 63 days respectively, while the ambient GAC filter took almost 3 times as long to acclimate (168 days), and the anthracite filters which received the same chemically adjusted water took almost 4 times as long (226 and 251 days, respectively). The accelerated acclimation in the treated GAC filters was likely due to physico-chemical oxidation via three potential mechanisms: (1) homogeneous oxidation of dissolved Mn(II) to Mn(III)/Mn(IV) oxides and the subsequent removal of oxides from solution through adherence to the GAC surface, (2) adsorption of dissolved Mn(II) to GAC and subsequent homogeneous or biological oxidation, or (3) formation of colloidal Mn(III)/Mn(IV) oxides and subsequent adsorption of dissolved Mn(II) to the Mn colloids. In the untreated GAC filter and all anthracite filters, which did not benefit from improved redox conditions or an active surface, physico-chemical mechanisms alone were insufficient for consistent Mn removal to less than 20 µg/L. Acclimation in these filters was delayed until a microbiome enriched with bacteria capable of biological nitrification and Mn oxidation evolved within the filters. The acclimated microbiome was consistent between GAC and anthracite filters and was significantly different from the non-acclimated microbiome (p < 0.001) initially formed during the early operation of the filters. Interestingly, treatment with NaOH, and NaOH and H2O2, which accelerated physico-chemical oxidation in GAC filters, was observed to delay the development of biological oxidation in anthracite filters, and thus deferred acclimation. Although some filters took longer to acclimate than others, once acclimation was reached all filters had a similar microbiome and were able to consistently remove Mn to below 20 µg/L.

Chemical recovery and browning of Nova Scotia surface waters in response to declining acid deposition.

Declining emissions of sulfur and nitrogen have curtailed acid deposition across large areas of North America and Europe. This has allowed many lakes to recover from acidification, with decreases in sulfate, increases in pH, and increases in alkalinity. But reduced acid deposition has not always coincided with chemical lake recovery. Surface waters in Nova Scotia did not exhibit clear evidence of recovery as recently as 2007, due in part to increasing organic acidity and slow replenishment of base cations. In an updated assessment with data collected as recently as 2019, we analyze water chemistry representing 81 lakes and rivers and two precipitation monitoring stations over up to 41 years. We find that Nova Scotia surface waters are now exhibiting signs of chemical recovery. We estimated the linear decrease in precipitation sulfate and nitrate yield at up to 0.31 and 0.18 kg ha-1 year-2, respectively, and the linear increase in precipitation pH at up to 0.014 year-1. Sulfate decreased in 60 of 62 lakes and 14 of 17 rivers (-0.0051 to -0.23 mg L-1 year-1), while pH increased in 55 of 64 lakes and 11 of 17 rivers (0.0015-0.072 year-1). Apparent colour increased in 54 of 62 lakes and 13 of 17 rivers (0.0026-3.9 Pt-Co year-1). We identified increasing aluminum trends in 46 of 61 lakes, and we show using size-exclusion chromatography that binding to organic and iron-based colloids may help to explain these trends. To the extent that increases in apparent colour are explained by chromophoric dissolved organic matter (DOM), they imply greater binding capacity for metals in surface waters, and greater capacity for DOM to stabilize metal (oxyhydr)oxide colloids.

Removal of acidic pharmaceuticals within a nitrifying recirculating biofilter.

The fate of pharmaceutically active compounds (PhACs) in wastewater treatment systems is an area of increasing concern. Little research has been done to understand this issue in rural or decentralized communities. The objective of this research was to examine the ability of a bench scale nitrifying recirculating biofilter (RBF) to remove four acidic PhACs: gemfibrozil, naproxen, ibuprofen and diclofenac from secondary treated municipal wastewater at concentrations of 20 and 200µg/L. The average removals in this study were between 92 and 99% for ibuprofen, 89 and 99% for naproxen, 62 and 92% for gemfibrozil and 40 and 76% for diclofenac, which is consistent with literature. Ibuprofen and naproxen were largely removed through biological transformation; whereas gemfibrozil and diclofenac showed more variable removal, likely due to both biological transformation and sorption processes. PhAC removal in the RBFs was repeatable between trials, robust and responsive to system upsets, and the presence of PhACs as a single compound versus mixtures had no impact on PhAC removal efficiency. In summary, this study indicates that RBFs as a nitrifying stage of a multi-stage filtration process could be a viable technology for removal of some acidic pharmaceuticals in small onsite wastewater treatment facilities.

Effect of coagulation and flocculation conditions on water quality in an immersed ultrafiltration process.

The removal of natural organic matter under variable coagulation and flocculation pretreatment conditions was evaluated for three surface waters in an immersed ultrafiltration (UF) process. Coagulation with alum, flocculation and UF treatment were conducted in a bench-scale test apparatus designed to simulate pilot- and full-scale water treatment systems. Variable coagulation and flocculation operating conditions were investigated, including coagulant dose, hydraulic retention time (HRT) and mixing intensity (e.g. velocity gradient). Treatment performance was evaluated by measuring specific water quality parameters in the permeate stream, including dissolved organic carbon (DOC), UV254 and true colour. Coagulant dose was found to be the most important variable for treatment performance with regard to permeate water quality, with significantly lower alum dosages required to achieve enhanced coagulation water quality targets than conventional filtration systems. Experiments conducted to evaluate variable flocculation stage HRT and applied velocity gradient demonstrated that traditional set points for these operating variables, applied in conventional filtration systems, may not be required in UF systems. In particular, optimized UF permeate water quality was found with reduced flocculation retention times (e.g. <10 minutes) and mixing intensities (e.g. < 100 s(-1)). The impact of intermittent air scour, or air sparging, operations in the UF process tank during operation was also evaluated. The use of air scour, tested as an intermittent operation at an applied velocity gradient of 50 s(-1) was found to significantly reduce DOC concentrations and UV254 measurements in the UF permeate stream when compared with UF operations without air scour.

Sequential UV- and chlorine-based disinfection to mitigate Escherichia coli in drinking water biofilms.

This study was designed to examine the potential downstream benefits of sequential disinfection to control the persistence of Escherichia coli under conditions relevant to drinking water distribution systems. Eight annular reactors (four polycarbonate and four cast iron) were setup in parallel to address various factors that could influence biofilm growth in distribution systems. Eight reactors were treated with chlorine, chlorine dioxide and monochloramine alone or in combination with UV to examine the effects on Escherichia coli growth and persistence in both the effluent and biofilm. In general, UV-treated systems in combination with chlorine or chlorine dioxide and monochloramine achieved greater log reductions in both effluent and biofilm than systems treated with chlorine-based disinfectants alone. However, during UV-low chlorine disinfection, E. coli was found to persist at low levels, suggesting that the UV treatment had instigated an adaptive mutation. During UV-chlorine-dioxide treatment, the E. coli that was initially below the detection limit reappeared during a low level of disinfection (0.2 mg/L) in the cast iron systems. Chloramine was shown to be effective in disinfecting suspended E. coli in the effluent but was unable to reduce biofilm counts to below the detection limit. Issues such as repair mechanism of E. coli and nitrification could help explain some of these aberrations. Improved understanding of the ability of chlorine-based disinfectant in combination with UV to provide sufficient disinfection will ultimately effect in improved management and safety of drinking water.

Biostability and disinfectant by-product formation in drinking water blended with UF-treated filter backwash water.

The overall objective of this study was to investigate the impact of blending membrane-treated water treatment plant (WTP) residuals with plant-filtered water on finished water quality in terms of biostability and disinfectant by-product (DBP) formation. Filter backwash water (FBWW) was treated with a pilot-scale ultrafiltration (UF) membrane to produce permeate that was blended with plant-finished water. The batch studies involved storing samples for a specified time with a disinfectant residual to simulate residence time in the distribution system. Both chlorinated and non-chlorinated FBWW streams were evaluated, and the experimental design incorporated free chlorine, monochloramine, and chlorine dioxide in parallel to a model system that did not receive a disinfectant dose. The results of the study found that blending 10% UF-treated FBWW with plant-filtered water did not have an impact on water biostability as monitored with heterotrophic plate counts (HPCs) or DBP concentrations as monitored by TTHM and HAA5 concentrations. However, the presence of preformed THM and HAA species found in chlorinated FBWW streams may result in higher levels of initial DBP concentrations in blended water matrices, and could have a significant impact on finished water quality in terms of meeting specific DBP guidelines or regulations.

A field study evaluation for mitigating biofouling with chlorine dioxide or chlorine integrated with UV disinfection.

The drinking water industry is continually seeking innovative disinfection strategies to control biofouling in transmission systems. This research, conducted in collaboration with the East Bay Municipal Utility District (EBMUD) in California, compared the efficacy of chlorine dioxide (ClO2) to free chlorine (Cl2) with and without pre-treatment with low-pressure ultraviolet (UV) light for biofilm control. An additional goal was to determine disinfection by-product (DBP) formation with each disinfection strategy. Annular reactors (ARs) containing polycarbonate coupons were used to simulate EBMUD's 90-mile aqueduct that transports surface water from a source reservoir to treatment facilities. ARs were dosed with chemical disinfectants to achieve a residual of 0.2 mg/L, which is a typical value mid-way in the aqueduct. The experiment matrix included four strategies of disinfection including UV/ClO2, ClO2, UV/Cl2 and Cl2. Two ARs acted as controls and received raw water (RW) or UV-treated water. The data presented show that the UV/ClO2 combination was most effective against suspended and attached heterotrophic (heterotrophic plate count, HPC) bacteria with 3.93 log and 2.05 log reductions, respectively. ClO2 was more effective than Cl2 at removing suspended HPC bacteria and similarly effective in biofilm bacterial removal. UV light alone was not effective in controlling suspended or biofilm bacteria compared to treatment with ClO2 or Cl2. Pre-treatment with UV was more effective overall for removal of HPC bacteria than treating with corresponding chemical disinfectants only; however, it did not lower required chemical dosages. Therefore, no significant differences were observed in DBP concentrations between ARs pre-treated with UV light and ARs not pre-treated. Disinfection with ClO2 produced fewer total trihalomethanes (TTHMs) and haloacetic acids (HAAs) than chlorination but did produce low levels of chlorite. These data indicate that replacing Cl2 with ClO2 would further control microbiological re-growth and minimize TTHM and HAA formation, but may introduce other DBPs.

Disinfectant efficacy of chlorite and chlorine dioxide in drinking water biofilms.

The drinking water industry is closely examining options to maintain disinfection in distribution systems. In particular this research compared the relative efficiency of the chlorite ion (ClO2-) to chlorine dioxide (ClO2) for biofilm control. Chlorite levels were selected for monitoring since they are typically observed in the distribution system as a by-product whenever chlorine dioxide is applied for primary or secondary disinfection. Previous research has reported the chlorite ion to be effective in mitigating nitrification in distribution systems. Annular reactors (ARs) containing polycarbonate and cast iron coupons were used to simulate water quality conditions in a distribution system. Following a 4 week acclimation period, individual ARs operated in parallel were dosed with high (0.25mg/l) and low (0.1mg/l) chlorite concentrations and with high (0.5 mg/l) and low (0.25mg/l) chlorine dioxide concentrations, as measured in the effluent of the AR. Another set of ARs that contained cast iron and polycarbonate coupons served as controls and did not receive any disinfection. The data presented herein show that the presence of chlorite at low concentration levels was not effective at reducing heterotrophic bacteria. Log reductions of attached heterotrophic bacteria for low and high chlorite ranged between 0.20 and 0.34. Chlorine dioxide had greater log reductions for attached heterotrophic bacteria ranging from 0.52 to 1.36 at the higher dose. The greatest log reduction in suspended heterotrophic bacteria was for high dose of ClO2 on either cast iron or polycarbonate coupons (1.77 and 1.55). These data indicate that it would be necessary to maintain a chlorine dioxide residual concentration in distribution systems for control of microbiological regrowth.

Effect of disinfectants on microbial ecology in model distribution systems.

This research was conducted to assess the impact of various disinfectants on bacterial water quality within model distribution systems (i.e. annular reactors). After colonization with non-disinfected water, annular reactors were treated with relatively low doses of chlorine (0.4 mg/l), chlorine dioxide (0.15 mg/l), or chloramines (0.9 mg/l). Under the tested conditions, bacterial inactivation varied as a function of disinfectant type (ranking by efficiency per mg of oxidant: ClO2 > Cl2 > ClNH2) and sample type (bulk water vs. biofilm). Depending on the disinfectant, the log inactivation of suspended and attached bacteria were 0.7-1.2 and 0.5-1.0, respectively. The characterization of microbial communities in drinking water can be performed using biochemical and/or molecular methods. In this study, biochemical tests were used, showing that pseudomonad and pseudomonad-like bacteria, as in other studies, were the most predominant micro-organisms (e.g. Pseudomonas fluorescens, Brevundimonas vescularis). The ratio Gram-positive to Gram-negative organisms was 1 to 3. No drastic differences were observed between the non-treated and disinfected pipes. Based on the bacteriological data presented in these experiments, chlorine dioxide represents an alternative to chlorine for certain distribution systems.

Optimizing settling conditions for treatment of liquid hog manure.

Sedimentation is a widely used separation method for treating agricultural waste. There are several chemical and biological characteristics, which can affect the settling behavior and liquid waste. The optimization of cation balances and potential for nitrification are among these processes. In addition to sedimentation, it can also affect the dewaterability of the samples. Liquid hog manure was used during the laboratory based experiments to investigate the effects of Ca2+ and Mg2+ ions and nitrification inhibition on the overall settling and dewatering characteristics. The results indicated that settling and dewatering characteristics improved during the course of the experiments. However, the improvement in settling and dewatering characteristics was inconsistent and not statistically significant. Cation addition in aerated reactor increased the highest settling velocity (94%). The improvement in dewaterability, as quantified by capillary suction time, was also not consistent. The greatest filterability observed in the supernatant was a capillary suction time of 40 s for a M:D ratio of 2:1. Initial NH 4 + concentration was more important than the nitrification inhibitor, as the presence of nitrification inhibitor increased the nitrification rate by over 300% because of the high initial NH 4 + concentration and low volatile suspended solid. The results from these experiments provide the basis for further field evaluation of cation optimization.

Impact of seasonal variation on treatment of swine wastewater.

Swine wastewater (agricultural wastewater) is normally stored in a storage holding tank for a certain time before released to the other treatment units, such as anaerobic lagoon and aerobic wetland. One of the characteristics for this treatment approach is that all the processes are open systems that are generally more passive in design and operation. As a consequence, seasonal variability including temperature and precipitation can have substantial impact on treatment efficacy and effluent water quality. This paper examines seasonal impacts of temperature on swine wastewater quality and treatment efficacy at a farm in East Leicester, Nova Scotia, Canada. During warm temperatures denitrification was noticeable in the anaerobic conditions, which would reduce the TSS removal rate from 76.6% in moderate temperatures to 42.1% in the warmest period recorded. Rainfall improved final effluent water quality, although this was shown to be through dilution rather than improvement of treatment efficacy. Following precipitation events the contaminant removals were negatively impacted in the aerobic lagoon, as BOD5 removal decreased from 61.6% before rainfall to 41.5% after rainfall, TSS from 71.4% to 59.3%, VSS from 73.4% to 59.3%, TKN from 59.9% to 42.1%, and NH4+ -N from 51.3% to 41.6%. In comparison to the aerobic conditions, the removal rates were increased for anaerobic condition with the rainfall dilution (e.g., TSS from 18.2% to 34.3%), which lead to an overall treatment improvement for the entire system. Thus the case study data presented in this paper provides an assessment of the operational and design issues that are particularly relevant for passive treatment systems that are used in the agriculture industry.

Treatment of drinking water residuals: comparing sedimentation and dissolved air flotation performance with optimal cation ratios.

Spent filter backwash water (SFBW) and clarifier sludge generally comprise the majority of the waste residual volume generated and in relative terms, these can be collectively referred to as combined filter backwash water (CFBW). CFBW is essentially a low-solids wastewater with metal hydroxide flocs that are typically light and slow to settle. This study evaluates the impact of adding calcium and magnesium carbonates to CFBW in terms of assessing the impacts on the sedimentation and DAF separation processes. Representative CFBW samples were collected from two surface water treatment plants (WTP): Lake Major WTP (Dartmouth, Nova Scotia, Canada) and Victoria Park WTP (Truro, Nova Scotia, Canada). Bench-scale results indicated that improvements in the CFBW settled water quality could be achieved through the addition of the divalent cations, thereby adjusting the monovalent to divalent (M:D) ratios of the wastewater. In general, the DAF process required slightly higher M:D ratios than the sedimentation process. The optimum M:D ratios for DAF and sedimentation were determined to be 1:1 and 0.33:1, respectively. It was concluded that the optimisation of the cation balance between monovalent cations (e.g., Na(+), K(+)) and added divalent cations (i.e., Ca(2+), Mg(2+)) aided in the settling mechanism through charge neutralisation-precipitation. The increase in divalent cation concentrations within the waste residual stream promoted destabilisation of the negatively charged colour molecules within the CFBW, thereby causing the colloidal content to become more hydrophobic.

Examination of plant performance and filter ripening with particle counters at full-scale water treatment plants.

Filter performance has traditionally been assessed using turbidity as the main water quality parameter. However interest in process optimization and the ability to accurately monitor filtration and particle removal has led to particle counting becoming increasingly more popular. The objective of this research was to evaluate filtration performance and filter ripening at four full-scale water treatment plants. Most of the plants investigated in this study were capable of achieving 2 log total particle removal as well as an effluent turbidity of 0.1 NTU. In some cases 2 log removal was achieved in the lower particle size ranges of 2-5 and 5-10 microm. Log removals in this study compare particle counts in the filtered and raw water. For water treatment plants that do not filter to waste, the ripening period following a filter backwash represents a time where the plant may be most vulnerable to breakthrough of waterborne pathogens. For the plants studied, the ripening period which was defined as the time required to reach peak particle removal and a turbidity of 0.1 NTU, were very similar in duration. The ripening period generally lasted for one hour after the backwash event had been completed. Because the times to reach 2 log total particle removal and 0.1 NTU are similar, the practice of using 0.1 NTU turbidity as a measure of filter ripening may be a useful benchmark for utilities that do not have particle counters.

Removal of easily biodegradable organic compounds by drinking water biofilms: analysis of kinetics and mass transfer.

This paper evaluates the rate of utilization of easily biodegradable organic compounds by drinking water biofilms. Tap water, which had been filtered through biologically active granular activated carbon, was used as an innoculum for biofilm growth in annular reactors (ARs). Synthetic cocktails of easily biodegradable material in the concentration range of 50-2,000 mgC/m3 were used as substrate for biofilm growth. Influent and effluent aggregate concentrations of biodegradable organic matter (BOM) were calculated by adding the measurable BOM components on a mass carbon basis. The aggregate BOM values were used for calculating the observed Damköhler number and Theile modulus (based on a reaction rate per unit surface area), which were used to determine whether external or internal mass transfer limited BOM removal. For all of the experimental trials, it was shown that neither external nor internal mass transfer limited BOM removal. Because the biofilms in this research are thin and the fact that mass transfer is not limiting, it was assumed that the bulk BOM concentration was approximately equal to the average BOM concentration in the biofilm. A linear model was obtained for the aggregate BOM flux and the product of the effluent BOM concentration and the biofilm density. The slope or the areal biodegradation rate (ka) for the aggregate BOM was 0.033 m/h, as determined through a linear regression.

Reversion of primary hyperfibrinogenolysis in patients with hormone-refractory prostate cancer using docetaxel.

Tumor-associated proteases play a major role in determining the biologic behavior and aggressiveness of prostate cancer. Several authors have described the association between the increased levels of urokinase plasminogen activator in the plasma and in the malignant prostatic tissue with the metastatic potential of prostate cancer. However, the direct effect of this activity in producing fibronogenolysis in patients with prostate cancer has not been addressed. To evaluate the role of chemotherapy in reversing fibrinogenolysis in patients with prostate cancer, eight patients with hormone-refractory prostate cancer, bleeding, and laboratory evidence of primary hyperfibrinogenolysis were treated with docetaxel. The drug was given 48 hr after initiation of all supportive measures. Laboratory data, including plasminogen, alpha 2-antiplasmin, and fibrinogen, were recorded before and after treatment. Prostate-specific antigen (PSA) was measured at the time of referral and before subsequent cycles (3 weeks). Five patients had resolution of the fibrinolytic process after one cycle of treatment with docetaxel. This was demonstrated by improvement in both the laboratory parameters and the bleeding episodes. Further follow-up showed stabilization of the hematologic parameters and reduction in PSA values in these patients. Two patients died from uncontrolled bleeding despite all supportive measures. One patient did not demonstrate response to this treatment in terms of normalization of the fibrinolytic indicators or reduction in PSA. Primary fibrinogenolysis associated with metastatic prostate cancer is a serious complication. Docetaxel appears to be effective in reversing this process in some hormone-refractory patients. Although this response appears to be due to antitumor activity, a direct effect on the fibrinolytic pathway induced by the tumor cannot be excluded. Further work in this area is warranted.

Angioimmunoblastic lymphadenopathy with dysproteinemia: emphasis on pathogenesis and treatment.

Angioimmunoblastic lymphadenopathy with dysproteinemia (AILD) is a rare lymphoproliferative disorder characterized by diffuse lymphadenopathy, fever, hepatosplenomegaly, hemolytic anemia, and polyclonal hypergammaglobulinemia. Morphologically, the involved lymph nodes demonstrate complete effacement of the normal architecture, prominent neovascularization and infiltration by immunoblasts and plasma cells. Other terms that have been used to describe this entity include diffuse plasmacytic sarcomatosis, immunoblastic lymphadenopathy, lymphogranulomatosis X, and immunologic aberrations in idiopathic reticulosis. Initially, AILD was thought to be a disease of B-cell origin that represented reactive immune response to unknown stimulus and high potential for malignant transformation. It is now evident that AILD in 80% of cases follows an aggressive course with short median survival, especially, if complete response with chemotherapy is not achieved. Immunologic and molecular studies have demonstrated that the majority of AILD cases are T-cell clonal disorders. Despite the numerous reports on the role of Epstein-Barr virus in this disorder, it is unknown whether the presence of this virus is associated with the immune defect that accompanies AILD, or whether it is a pathogenetic factor. In contrast to non-Hodgkin's lymphomas, a stage is not usually assigned to the patient since the disease is systemic in nature, subsequently, parameters such as extent of disease and tumor bulk used to identify high-risk patients with non-Hodgkin's lymphomas, do not appear to correlate with disease activity or prognosis in AILD. Treatment of AILD has been unsatisfactory, with approximately 25% of patients achieving complete and sustained remission when combined chemotherapy agents are used. This article is devoted to a discussion of the different manifestations, suggested pathogenesis, and treatment of AILD.

Recurrent warfarin-induced skin necrosis in kindreds with protein S deficiency.

Warfarin-induced skin necrosis is a rare complication of anticoagulant treatment. The incidence of this complication is undetermined, but it has been estimated to occur between 1:100 and 1:10,000 of patients treated with anticoagulants. Coumarin skin necrosis occurs almost exclusively in patients with venous thrombosis between the 3rd and 10th day after beginning anticoagulation. Although protein C deficiency is the most common underlying hypercoagulable state reportedly associated with warfarin skin necrosis, very few cases have been linked to congenital protein S deficiency. This article addresses the association of hereditary protein S deficiency and warfarin skin necrosis, and provides suggestions for management.

The spectrum of mucosa-associated lymphoid tissue lesions in pediatric patients infected with HIV: A clinicopathologic study of six cases.

Mucosa-associated lymphoid tissue (MALT) lesions in nonimmunocompromised individuals include reactive lymphoid proliferations and both low- and high-grade lymphoid neoplasms. These lesions occur at extranodal mucosal sites, such as the gastrointestinal tract, bronchus, salivary gland, and other locations. The spectrum of MALT lesions in children with HIV infection had not been previously described. In this study, six cases that demonstrated the spectrum of MALT lesions in pediatric patients, aged 28 months to 23 years, who had HIV infection were described. Half the patients acquired the infection perinatally, and half acquired it by transfusion. Mucosal sites of involvement included the salivary gland (4 patients), bronchiolar mucosa (2 patients), and oropharyngeal mucosa (1 patient). One patient had lesions in lung and oropharynx sequentially; all others had involvement of solitary sites. The histologic diagnoses included myoepithelial sialadenitis (MESA), MESA with low-grade MALT lymphoma, typical low-grade MALT lymphoma, diffuse large cell lymphoma (DLCL), and atypical pulmonary lymphoid hyperplasia and lymphoid interstitial pneumonitis complex. The two cases of high-grade DLCL were confined to mucosal sites (tonsil and parotid); in one of these patients, a previous biopsy specimen showed a MALT lesion with low-grade features. In two cases, quantitation of the Epstein-Barr virus (EBV) genome by the polymerase chain reaction showed a very high copy number in peripheral blood mononuclear cells but a low copy number in the MALT lesion, which suggested that MALT lesions may not be directly associated with EBV infection. Two patients who had high-grade tumors (DLCL) were successfully treated with chemotherapy and radiation therapy. The remaining patients, all of whom had low-grade MALT lesions, received either corticosteroids or alpha-interferon or no specific therapy; in all patients, the lesions followed an indolent clinical course. Clinicians and pathologists should be alert to the possibility that MALT lesions, including MALT lymphomas, may be present in children who have AIDS.

Molecular heterogeneity in acute leukemia lineage switch.

Six cases of acute leukemia that underwent lineage switch from acute lymphocytic leukemia to acute myelogenous leukemia are reported. The mean age of the patients was 24 years, time to conversion was 36 months, and survival after conversion was only 3 months. Of the three cases which showed abnormal metaphases at both diagnosis and conversion, two (cases 2, 5) showed related cytogenetic abnormalities, and the third showed (case 3) independent chromosomal changes. Molecular analysis for immunoglobulin heavy chain and T-cell receptor beta chain genes showed that five of the six cases had rearrangement of at least one of these lymphoid associated genes at conversion to acute myelogenous leukemia. The single case (case 3) in which there were no lymphoid gene rearrangements at conversion was also the only case in which independent karyotypic abnormalities at diagnosis and conversion were demonstrated. Our findings suggest that lineage switch can represent either relapse of the original clone with heterogeneity at the molecular level or the emergence of a second new leukemic clone without molecular heterogeneity.