Assessing bottled water nitrate concentrations to evaluate total drinking water nitrate exposure and risk of birth defects.

Previous epidemiologic studies of maternal exposure to drinking water nitrate did not account for bottled water consumption. The objective of this National Birth Defects Prevention Study (NBDPS) (USA) analysis was to assess the impact of bottled water use on the relation between maternal exposure to drinking water nitrate and selected birth defects in infants born during 1997-2005. Prenatal residences of 1,410 mothers reporting exclusive bottled water use were geocoded and mapped; 326 bottled water samples were collected and analyzed using Environmental Protection Agency Method 300.0. Median bottled water nitrate concentrations were assigned by community; mothers' overall intake of nitrate in mg/day from drinking water was calculated. Odds ratios for neural tube defects, limb deficiencies, oral cleft defects, and heart defects were estimated using mixed-effects models for logistic regression. Odds ratios (95% CIs) for the highest exposure group in offspring of mothers reporting exclusive use of bottled water were: neural tube defects [1.42 (0.51, 3.99)], limb deficiencies [1.86 (0.51, 6.80)], oral clefts [1.43 (0.61, 3.31)], and heart defects [2.13, (0.87, 5.17)]. Bottled water nitrate had no appreciable impact on risk for birth defects in the NBDPS.

Intellectual property management at the National Animal Science Research Institute in India: A case study.

AIM: The National Institute of Veterinary Epidemiology and Disease Informatics is an animal science research institute under the aegis of the Indian Council of Agricultural Research. The intellectual property management system (IPMS) of the institute oversees technology creation, protection, and transfer/commercialization. This study reviews the effectiveness of the IPMS using traditional strengths, weaknesses, opportunities, and threats (SWOT) evaluation. MATERIALS AND METHODS: A comprehensive repository was developed to compile the SWOT pertaining to the IPMS based on relevant document reviews and the inputs of experts and stakeholders. The repository was shared among scientists of the institute for rating. The rating process revealed the top ten key SWOT associated with the structure and operation of the IPMS. The weighted SWOT matrix technique was used to identify the best strategies to improve and develop the IPMS further. This included strategies derived from the best combinations of key strengths and opportunities (S-O strategies), key weaknesses and opportunities (W-O strategies), key strengths and threats (S-T strategies), and key weaknesses and threats (W-T strategies). RESULTS: The top-ranked strengths included "possession of patented technology" and "state-of-the-art biosafety laboratory facilities," while "lack of in-house faculty with legal expertise in intellectual property rights (IPR)" and "lack of technology incubation facilities" were the key weaknesses. The key opportunities included "external funding for research projects" and "market demand for onsite diagnostic tools." The major threats were "lack of market for veterinary diagnostics" and "broad-based patents on research tools and technologies." CONCLUSION: The strengths of the system, such as a state-of-the-art biosafety laboratory and technology-marketing collaboration with Agrinnovate India Ltd., could be employed effectively to gain from the opportunities tendered by the market demand for on-site disease diagnostic tools (S-O strategies). The limitation arising from a dearth of technical staff could be overcome by technological backstopping through international linkages in the area of disease monitoring and surveillance. Funding from externally supported projects could also be utilized for recruitment of personnel (W-O strategies). Limitations arising from the combination of inadequate in-house IPR expertise and the threat arising from broad-based patents on research tools warrant vigilance (W-T strategies).

A New Method to Determine the Transmembrane Conformation of Substrates in Intramembrane Proteolysis by Deep-UV Resonance Raman Spectroscopy.

We present a new method based on deep-UV resonance Raman spectroscopy to determine the backbone conformation of intramembrane protease substrates. The classical amide vibrational modes reporting on the conformation of just the transmembrane region of the substrate can be resolved from solvent exchangeable regions outside the detergent micelle by partial deuteration of the solvent. In the presence of isotopically triple-labeled intramembrane protease, these amide modes can be accurately measured to monitor the transmembrane conformation of the substrate during intramembrane proteolysis.

Angioimmunoblastic lymphadenopathy. Its occurrence with meningeal involvement.

A case of angioimmunoblastic lymphadenopathy with involvement of the leptomeninges and the lumbosacral nerve roots was studied. This condition seems related to malignant lymphoma, and clinical improvement occurred with administration of systemic corticosteroids.

Lysis of paroxysmal nocturnal hemoglobinuria erythrocytes by acid-activated serum.

Erythrocytes from paroxysmal nocturnal hemoglobinuria patients (PNH-E) are much more susceptible to lysis by acid-activated human serum than normal human erythrocytes. Acidification of normal human serum to pH 6.4 in the absence of erythrocytes generates this lytic activity independently of the alternative pathway of complement activation. A shift of pH of a mixture of purified human C5 and C6 to 6.4 at 0 degrees C generates a similar activity C(56)a that lyses PNH-E together with C7-C9 much more efficiently than normal erythrocytes. Since acid-activation of normal human serum occurs in the absence of C3, the acid-activated C56 appears to be the lytic principle in acidified human serum.

Cutaneous infection due to a rough variant of Mycobacterium marinum.

Spreading lesions clinically resembling lymphangitic sporotrichosis developed on the right arm and chest of a 60-year-old man with chronic lymphocytic leukemia. Acid-fast bacilli were seen in exudates from lesions and in biopsies, and were cultured from them. The isolant grew initially as a yellowish-orange scotochromogen on Lowenstein-Jensen medium at room temperature and at 35 C., but failed to grow at 37 C. It failed to grow on 7-H-10 medium. On repeated subculturing over a 2-year period it gradually converted to a photochromogen. Histologically, there was ulceration with extensive acute and chronic inflammation with fibrosis. Organisms occurred intracellularly as dense, compact, cigar-like packets resembling lepara bacilli. The appeared to have a predilection for the nucleus. The patient was anergic to PPD S, B, Y and G, and lacked antibodies to BCG phosphoglycolipids. The mycobacteriosis was alleviated by combined INH and ethambutol therapy. The isolant was identified as a rough variant of Mycobacterium marinum. It may have been transmitted by an insect vector.

Translocation (6;9)(p23;q34) in acute nonlymphocytic leukemia.

A consistent chromosomal abnormality t(6;9)(p23;q34) was demonstrated in the bone marrow or unstimulated peripheral blood cultures of two patients with acute nonlymphocytic leukemia (ANLL). Only two additional cases with ANLL and a similar cytogenetic finding have been reported, indicating that this translocation may represent another chromosomal abnormality specifically associated with ANLL.

Chromosome abnormalities in acquired idiopathic sideroblastic anemia with subsequent leukemic transformation.

Chromosomal abnormalities were demonstrated in the bone marrow cultures of two patients with acquired idiopathic sideroblastic anemia (AISA). Both patients subsequently experienced leukemic transformation and developed acute myelomonocytic leukemia (type M4). A review of the literature revealed that approximately 40% of the AISA cases manifest chromosomal abnormalities, of which 20.5% underwent leukemic conversion.

Histoplasmosis of skin and lymph nodes and chronic lymphocytic leukemia.

Nodular skin and cervical lymph node lesions of histoplasmosis, unassociated with systemic symptoms of the infection, developed in a 63-year-old man with untreated chronic lymphocytic leukemia. The histologic patterns in both the skin and lymph node were those of a lymphoproliferative disorder, but Histoplasma organisms were found within a few scattered histiocytes after a careful search. The subtle clinical and pathologic presentation might lead one to overlook the organisms and to believe that the leukemic process had progressed, resulting in potentially dangerous systemic involvement of histoplasmosis and unnecessary chemotherapy for his leukemic process. Complete remission of histoplasmosis was obtained with amphotericin B therapy.

Muscular Dystrophy Surveillance Tracking and Research Network (MD STARnet): case definition in surveillance for childhood-onset Duchenne/Becker muscular dystrophy.

The Muscular Dystrophy Surveillance Tracking and Research Network (MD STARnet) is a multisite collaboration to determine the prevalence of childhood-onset Duchenne/Becker muscular dystrophy and to characterize health care and health outcomes in this population. MD STARnet uses medical record abstraction to identify patients with Duchenne/Becker muscular dystrophy born January 1, 1982 or later who resided in 1 of the participating sites. Critical diagnostic elements of each abstracted record are reviewed independently by >4 clinicians and assigned to 1 of 6 case definition categories (definite, probable, possible, asymptomatic, female, not Duchenne/Becker muscular dystrophy) by consensus. As of November 2009, 815 potential cases were reviewed. Of the cases included in analysis, 674 (82%) were either ''definite'' or ''probable'' Duchenne/Becker muscular dystrophy. These data reflect a change in diagnostic testing, as case assignment based on genetic testing increased from 67% in the oldest cohort (born 1982-1987) to 94% in the cohort born 2004 to 2009.

Comparison of nitrate levels in raw water and finished water from historical monitoring data on Iowa municipal drinking water supplies.

Nitrate contamination of water sources is a concern where large amounts of nitrogen fertilizers are regularly applied to soils. Ingested nitrate from dietary sources and drinking water can be converted to nitrite and ultimately to N-nitroso compounds, many of which are known carcinogens. Epidemiologic studies of drinking water nitrate and cancer report mixed findings; a criticism is the use of nitrate concentrations from retrospective drinking water data to assign exposure levels. Residential point-of-use nitrate data are scarce; gaps in historical data for municipal supply finished water hamper exposure classification efforts. We used generalized linear regression models to estimate and compare historical raw water and finished water nitrate levels (1960s-1990s) in single source Iowa municipal supplies to determine whether raw water monitoring data could supplement finished water data to improve exposure assessment. Comparison of raw water and finished water samples (same sampling date) showed a significant difference in nitrate levels in municipalities using rivers; municipalities using other surface water or alluvial groundwater had no difference in nitrate levels. A regional aggregation of alluvial groundwater municipalities was constructed based on results from a previous study showing regional differences in nitrate contamination of private wells; results from this analysis were mixed, dependent upon region and decade. These analyses demonstrate using historical raw water nitrate monitoring data to supplement finished water data for exposure assessment is appropriate for individual Iowa municipal supplies using alluvial groundwater, lakes or reservoirs. Using alluvial raw water data on a regional basis is dependent on region and decade.

Mitigation of Rayleigh and Raman spectral interferences in multiway calibration of excitation-emission matrix fluorescence spectra.

A weighted parallel factor analysis (W-PARAFAC) model is applied to excitation-emission matrix (EEM) fluorescence spectra of carbamate pesticides to aid with calibration in the presence of Raman scattering. Traditional PARAFAC inefficiently models the Raman scattering, resulting in prediction and calibration errors when a significant background is present. Four different weighting strategies were investigated and compared with subtraction of the appropriate sample background. Using a binary weighting strategy produced superior results, compared with a continuous distribution of weights. Further choice of weighting strategies, which are optimized to include either maximum analyte signal or to exclude a maximum amount of background scattering, is dependent on the degree of overlap and relative signal intensity.

Deferoxamine (Desferal)-induced toxic retinal pigmentary degeneration and presumed optic neuropathy.

Eight patients (16 eyes) developed ocular toxicity while undergoing intravenous deferoxamine mesylate (Desferal) chelation therapy for transfusional hemosiderosis. Presenting symptoms included decreased visual acuity, color vision abnormalities, and night blindness. Six patients presented as presumed retrobulbar optic neuropathy demonstrating central scotomas and color vision abnormalities. The remaining two patients presented with pigmentary changes confined either to the macula or equator. Following cessation of therapy, vision improved in all but four eyes, which did not attain their pretreatment visual acuity. Optic neuropathy resolved in all cases. However, follow-up revealed development of retinal pigmentary degeneration in seven patients, involving the macula in six and the equatorial retina in one. Fluorescein angiography and electrophysiological tests suggested toxicity at the level of retinal pigment epithelium and photoreceptors.

Microcytic hypochromic anemia associated with renal cell carcinoma.

Anemia, frequently hypochromic and microcytic, occurs in approximately one third of patients with renal cell carcinoma. We have described a patient with classic iron deficiency anemia and renal cell carcinoma whose blood picture reverted to normal after removal of the tumor. Abundant hemosiderin in the tumor cells is evidence that tumor cells removed iron from the circulation, causing the iron deficiency anemia.

An anti-i biphasic hemolysin in chronic paroxysmal cold hemoglobinuria.

Paroxysmal cold hemoglobinuria (PCH) was diagnosed in an elderly patient with a history of chronic lymphocytic leukemia. In this case, the Donath-Landsteiner antibody demonstrated anti-i specificity rather than the more commonly reported anti-P specificity. This unusual case of a biphasic hemolysin with anti-i specificity emphasizes the importance of performing a Donath-Landsteiner test when presented with serological or clinical findings that are suggestive of PCH.

Energy dispersive x-ray microanalysis of mitochondrial deposits in sideroblastic anemia.

Energy dispersive x-ray microanalysis was used to analyze mitochondrial and lysosomal iron-containing deposits in sideroblastic anemia. Although it has been previously known that these deposits contain iron by inference from Prussian blue staining, the possible presence of other cations as well as the nature of the anions present has not been identified. The results show that the mitochondrial deposits in erythroid cells have peaks for iron and phosphorus indicating that they do not represent calcifications which commonly occur following injury and that the principal anion may be phosphorus. Studies of hemosiderin and ferritin aggregates in lysosomes of macrophages in the same bone marrow samples again reveal similar peaks for iron and phosphorus. The results also indicate the probable similarity of mitochondrial and macrophage deposists although ferritin itself was never identified in the mitochondrial deposits. The results illustrate the potential of this method for diagnostic and investigative pathology.

A molecular basis for hemoglobin-H disease in American blacks.

We have applied gene counting and restriction endonuclease mapping techniques to the study of two American black families in which there were one or more cases of HbH disease. We found deletions of three of the four normal alpha-globin genes in individuals with HbH disease. In two of these individuals, the chromosome containing the single alpha gene could have originated by crossing over between mispaired alpha genes, resulting in a deletion of about 4.2 kilobases (kb).