Microsatellite DNA mutations in double-crested cormorants (Phalacrocorax auritus) associated with exposure to PAH-containing industrial air pollution.

Hamilton Harbour, Ontario, Canada is one of the most polluted sites on the Great Lakes, and is subject to substantial airborne pollution due to emissions from both heavy industry and intense vehicle traffic. Mutagenic Polycyclic aromatic hydrocarbons (PAHs) are present at very high concentrations in the air and sediment of Hamilton Harbour. We used five variable DNA microsatellites to screen for mutations in 97 families of Double-crested Cormorants (Phalacrocorax auritus) from three wild colonies, two in Hamilton Harbour and one in cleaner northeastern Lake Erie. Mutations were identified in all five microsatellites at low frequencies, with the majority of mutations found in chicks from the Hamilton Harbour site closest to industrial sources of PAH contamination. Microsatellite mutation rates were 6-fold higher at the Hamilton Harbour site closest to the industrial sources of PAH contamination than the other Hamilton Harbour site, and both were higher than the reference colony. A Phase I metabolite of the PAH benzo[a]pyrene identified by LC-MS/MS in bile and liver from Hamilton Harbour cormorant chicks suggests that these cormorants are exposed to and metabolizing PAHs, highlighting their potential to have caused the observed mutations.

Phase III randomized study of cisplatin versus paclitaxel versus cisplatin and paclitaxel in patients with suboptimal stage III or IV ovarian cancer: a gynecologic oncology group study.

PURPOSE: To assess progression-free survival (PFS) and overall survival (OS) in patients with suboptimally debulked epithelial ovarian cancer receiving cisplatin (100 mg/m(2)) or 24-hour infusion paclitaxel (200 mg/m(2)) or the combination of paclitaxel (135 mg/m(2)) followed by cisplatin (75 mg/m(2)). PATIENTS AND METHODS: After stratification for disease measurability, patients were randomized to receive six cycles of one of the treatments every 3 weeks. If measurable, complete response (CR) or partial response (PR) was determined. RESULTS: Six hundred fourteen of 648 patients who entered onto the trial were eligible. Monotherapies were discontinued more frequently (cisplatin because of toxicity or patient refusal [17%], and paclitaxel because of progression [20%]) compared with the combination therapy (7% and 6%, respectively). Neutropenia, fever, and alopecia were more severe with paclitaxel-containing regimens; whereas anemia, thrombocytopenia, neurotoxicity, nephrotoxicity, and gastrointestinal toxicity were more severe with cisplatin-containing regimens. The CR/PR rates on paclitaxel monotherapy were significantly lower compared with the cisplatin regimens (42% v 67%, respectively; P <.001). The relative hazard (RH) of first progression or death was significantly greater among those randomized to paclitaxel (RH = 1.41; 95% confidence interval [CI], 1.15 to 1.73; P <.001) when compared with cisplatin; however, RH did not differ significantly between the two cisplatin regimens (RH = 1.06; 95% CI, 0.895 to 1.30). Relative to cisplatin, the death rate on paclitaxel was 15% greater (RH = 1.15; 95% CI, 0. 929 to 1.42), and the death rate on the combination treatment was 1% less (RH = 0.99; 95% CI, 0.795 to 1.23). These differences among treatment groups were not statistically significant (P =.31). CONCLUSION: Cisplatin alone or in combination yielded superior response rates and PFS relative to paclitaxel. However, OS was similar in all three arms, and the combination therapy had a better toxicity profile. Therefore, the combination of cisplatin and paclitaxel remains the preferred initial treatment option.

Syme amputation for the treatment of fibular deficiency. An evaluation of long-term physical and psychological functional status.

BACKGROUND: Syme amputation is an accepted treatment for fibular deficiency. With improvement in limb-lengthening procedures, there has been renewed interest in limb salvage for these patients. The purpose of the present study was to evaluate the physical and psychological results in ten young adults who had had a Syme amputation for the treatment of fibular deficiency when they were children. METHODS: The evaluation consisted of physical examination, prosthetic assessment, psychological testing, and physical performance testing of knee extension and flexion with use of a Cybex-II dynamometer. RESULTS: Five patients reported no difficulty with the involved limb since the Syme amputation, four had had minor secondary procedures (three medial distal femoral or proximal tibial hemiepiphyseodeses, one reconstruction with an autologous patellar ligament graft, one revision of the stump, and one tibial osteotomy) on the affected extremity, and one had mild instability of the knee that had been treated nonoperatively. All ten patients had an appropriate, functional Syme prosthesis, and none reported difficulty with walking or running. On psychological testing, this group generally did not differ from the norm with regard to occupational satisfaction, personal growth, relationships with family members and peers, and recreational behavior. The patients' overall assessment of self-reported quality of life and self-esteem was similar to that of normative adult samples. In general, these patients were leading active, productive lives and had always done so. CONCLUSIONS: On the basis of the results of this study, we concluded that young adults who have had a Syme amputation apparently are not limited in their ability to pursue and achieve personal goals. In order to justify recommending limb salvage rather than early Syme amputation for the treatment of fibular deficiency, the results of multistaged lengthening and reconstruction would have to match the functional, psychological, and cost-effective results for the patients whom we studied, who had had a Syme amputation.

Lumbar lordosis. Effects of sitting and standing.

STUDY DESIGN: The effect of sitting versus standing posture on lumbar lordosis was studied retrospectively by radiographic analysis of 109 patients with low back pain. OBJECTIVE: To document changes in segmental and total lumbar lordosis between sitting and standing radiographs. SUMMARY OF BACKGROUND DATA: Preservation of physiologic lumbar lordosis is an important consideration when performing fusion of the lumbar spine. The appropriate degree of lumbar lordosis has not been defined. METHODS: Total and segmental lumbar lordosis from L1 to S1 was assessed by an independent observer using the Cobb angle measurements of the lateral radiographs of the lumbar spine obtained with the patient in the sitting and standing positions. RESULTS: Lumbar lordosis averaged 49 degrees standing and 34 degrees sitting from L1 to S1, 47 degrees standing and 33 degrees sitting from L2 to S1, 31 degrees standing and 22 degrees sitting from L4 to S1, and 18 degrees standing and 15 degrees sitting from L5 to S1. CONCLUSION: Lumbar lordosis while standing was nearly 50% greater on average than sitting lumbar lordosis. The clinical significance of this data may pertain to: 1) the known correlation of increased intradiscal pressure with sitting, which may be caused by this decrease in lordosis; 2) the benefit of a sitting lumbar support that increases lordosis; and 3) the consideration of an appropriate degree of lordosis in fusion of the lumbar spine.

The frequency of fungal involvement in abnormal vocal cord biopsy specimens.

Finding an unsuspected fungal infection of the true vocal cord prompted a retrospective study of abnormal vocal cords received as surgical specimens. Of 30 cases initially diagnosed histologically as either inflammation or hyperkeratosis, two (in addition to the index case) contained fungal elements visible on special stains. None of the patients had systemic mycoses on examination or on follow-up. Local excision apparently cured all lesions. Fungi may cause more vocal cord lesions than previously recognized and cannot be well visualized on routine sections.

Inservice education needs in geronotological nursing.

This study in the field of gerontological nursing, identified perceived geronotological learning needs of RNs employed in long term care (LTC) facilities in Alberta to obtain a data base upon which the planning and development of inservice education in gerontological nursing could be based. Several conclusions were reached. Many highly perceived gerontological learning needs exist among RNs working in LTC in Alberta. Perceived learning needs remained high throughout the stages of resident flow. Priorities for program development in gerontological nursing were established. Although inservice education attendance over the previous two years was low, programs that address these needs should be available on a regular basis. Time to attend inservice programming is a problem that needs to be addressed. This study has provided useful information upon which inservice programming in gerontological nursing in LTC may be based.

Binding of purified and radioiodinated capsular polysaccharides from Cryptococcus neoformans serotype A strains to capsule-free mutants.

Strains 6, 15, 98, 110, and 145 of Cryptococcus neoformans serotype A vary in capsule size, animal virulence, and susceptibility to in vitro phagocytosis. The isolated capsular polysaccharides (CPSs) differ in monosaccharide composition ratios and molecular size, as determined by gel filtration. The purpose of this investigation was to characterize the binding of CPSs to capsule-free mutants of C. neoformans and to examine CPSs from these strains for differences in their ability to bind, to determine whether such differences might explain the variation in the pathobiology of these strains. CPSs were partially periodate oxidized, tyraminated, iodinated with 125I, and used in binding studies with two capsule-free mutants of C. neoformans, strain 602 and Cap59. Binding was specific for yeast species and for polysaccharide and was saturable, which is consistent with a receptor-mediated mechanism of attachment. Binding occurred rapidly and was only slowly reversible. Binding was also independent of pH from pH 5.5 to 8, of cation concentrations, and of competition by sugars up to 1.0 M concentrations. Only a portion of CPS was capable of binding, and strains varied in the extent to which their CPS bound. CPS-15-IV (peak IV was the major polysaccharide peak on DEAE-cellulose chromatography of CPS from strain 15) had the highest proportion of binding (40%), followed by CPS from strains 98, 6, 145, 110, and 15-III (peak III was an earlier eluting fraction of CPS from strain 15). The CPSs differed similarly in their ability to competitively inhibit binding. Treatment of CPS, but not yeast cells, with proteinase XIV abolished binding without altering the CPS gross structure. Treatment of yeast cells with proteases, heat, or formaldehyde did not alter binding, and both strain 602 and Cap59 bound CPS similarly. Binding to encapsulated yeast cells was minimal.

Antibiotic residue release at the beginning of lactation following dry cow therapy.

In response to farmer complaints about unfair penalties, for the presence of inhibitory substances in early lactation following the use of dry-cow antibiotic therapy, a two-part study was carried out to try and establish why these unexplained grades occur. A survey of instructions supplied with each of 13 registered dry-cow products suggested that the directions for drug use were in some cases inappropriate for long-acting antibiotics. A residue release study was conducted at the beginning of lactation following antibiotic therapy at various times during the dry period. The results showed, for the-three dry-cow preparations studied, that treatment during the dry period, especially within six weeks of calving, could lead to detectable residues in milk from treated quarters.

Strain variation in antiphagocytic activity of capsular polysaccharides from Cryptococcus neoformans serotype A.

Strains of Cryptococcus neoformans vary in resistance to phagocytosis in vitro. The binding of isolated capsular polysaccharide (CPS) to a capsule-free mutant of C. neoformans confers resistance to phagocytosis. The importance of capsule composition to differences among strains in susceptibility to phagocytosis was evaluated. CPSs from five strains of C. neoformans serotype A, designated 6, 15, 98, 110, and 145, which had previously been isolated and characterized as to molecular size, composition, and binding properties, were evaluated for relative antiphagocytic potencies. In the presence of 5% normal isologous serum, murine thioglycolate-elicited peritoneal macrophages phagocytized (i.e., attached to or engulfed) 80% of 51Cr-labeled cells of C. neoformans 602, a capsule-free mutant. Added CPS inhibited the uptake of these yeast cells. CPS from strain 110 was most potent, followed in decreasing order of inhibitory activity by CPSs from strains 6, 145, 98, and 15. The presence of 100 micrograms of strain 110 CPS per ml reduced uptake of cells of strain 602 from 80 to 50%. CPS had no effect on the uptake of 51Cr-labeled Saccharomyces cerevisiae. Cells of strain 602 that were preincubated with CPS and then washed were more resistant to phagocytosis than nonpretreated control cells, indicating the importance of bound, not free, CPS. Added CPS did not affect the uptake of wild-type, encapsulated cells of C. neoformans. Addition of endotoxin had no effect on phagocytosis. CPSs from strains of C. neoformans serotype A varied widely in their abilities to inhibit the uptake of capsule-free cells. The antiphagocytic activity of CPS did not correlate with the ability to bind to capsule-free mutant but was somewhat related to the capsule size of the strain from which the CPS was isolated.

Strain variation in composition and molecular size of the capsular polysaccharide of Cryptococcus neoformans serotype A.

The capsule of Cryptococcus neoformans is an important virulence factor. In this investigation capsular polysaccharides (CPSs) were isolated by ethanol precipitation from culture filtrates of C. neoformans serotype A strains 6, 15, 98, 110, and 145. Capsule sizes on India ink examination ranged from barely perceptible (strain 15) to greater than the diameter of the yeast cell (strain 6); the others were intermediate in size. On ion-exchange chromatography on DEAE-cellulose each CPS eluted at 0.2 M NaCl; CPS of strain 15 had two major peaks, designated III and IV. On gel-permeation chromatography CPSs of strains 6, 98, 110, and 145 eluted at the void volume of Sepharose CL-2B in the presence or 0.1 M EDTA, while the CPS of strain 15 eluted in two peaks. Sephacryl S-1000 resolved CPSs of all five strains in the following order, from largest to smallest molecular size: 145 greater than 110 greater than 98 greater than 6 much greater than 15. All five CPSs contained mannose, xylose, and glucuronic acid, while the carboxyl-reduced CPS of strain 110 also contained a large percentage of an inositol-like compound. The CPS of strain 110 contained approximately 30% uronic acid by weight, while the others had 15 to 20%. The composition of peak IV from the CPS of strain 15 resembled those of the other strains; peak III of strain 15 contained a substantial amount of galactose. Each CPS contained less than 0.2% protein by weight. The significant differences in molecular size and sugar composition among CPSs of these strains of C. neoformans serotype A may partially explain strain differences in virulence and biological properties of the organism.