Guideline-discordant androgen deprivation therapy in localized prostate cancer: patterns of use in the medicare population and cost implications.

Background Androgen deprivation therapy (ADT) in localized prostate cancer improves overall survival and is recommended by National Comprehensive Cancer Network guidelines in certain situations. However, ADT is without benefit in other situations and can actually cause harm. This study examines recent trends in the ADT use and quantifies the cost of guideline-discordant ADT. Patients and methods Patients, aged 66-80 years, in the Surveillance Epidemiology and End Results-Medicare database with non-metastatic prostate cancer diagnosed between 2004 and 2007 were included for analysis. Prostate-specific antigen, Gleason score, and stage were used to define D'Amico risk categories. Logistic regression was used to examine factors associated with guideline-discordant ADT. Annual direct cost was estimated using 2011 Medicare reimbursement for ADT. Results Of 28 654 men included, 12.4% received guideline-discordant ADT. In low-risk patients, 14.9% received discordant ADT, mostly due to simultaneous ADT with radiation. Discordant use was seen in 7.3% of intermediate and 14.9% of high-risk patients, mostly from ADT as primary therapy. The odds of receiving guideline-discordant ADT decreased over time (2007 versus 2004; OR 0.69; 95% CI 0.62-0.76). The estimated annual direct cost from discordant ADT is $42 000 000. Conclusion Approximately one in eight patients received ADT discordant with published guidelines. Elimination of discordant use would result in substantial savings.

Production of recombinant protein Pap31 and its application for the diagnosis of Bartonella bacilliformis infection.

Tropical bartonellosis is a highly fatal epidemic and endemic infectious disease that occurs throughout the communities of the Andes Mountains in South America. The disease is caused by the facultative intracellular bacteria, Bartonella bacilliformis. The emergence of bartonellosis in new geographic areas and an increase in the number of reported cases suggest the need for a rapid test for epidemiologic study and investigation of the disease burden. The objective of this research is to develop a rapid serologic diagnostic test using recombinant antigens to overcome the limitations of the current standard IFA technique for laboratory diagnosis. Western blot analysis with patient sera of whole cell lysate separated on a 2D gel identified Pap31 as a dominant antigen. PCR primers were designed according to the sequence of ATCC strain 35685 to amplify the gene coding for Pap31 from a local isolate (HOSP 800-09, Peru). The amplicon was subsequently cloned into pET24a, adding the T7 tag, and expressed in E. coli. Patient sera with different IFA titers confirmed the diagnostic band of 31 kDa on a Western blot of SDS-PAGE. The performance of affinity-purified recombinant Pap31 (rPap31) was also evaluated in an ELISA format with 137 patient sera of known IFA titers. The range of ELISA reading from positive sera did not overlap with the range of those from negative sera, suggesting the potential application of rPap31 in both ELISA for high throughput regional hospital settings and in the construction of handheld rapid tests for rural clinical sites.

Using an interview guide to identify effective nurse managers: phase II, outcomes.

The investigators report validation of a survey tool called the Interview Guide to assist in the selection of nurses who will be effective as managers. Nurse administrators rated nurse managers at six months and two years after hire. The Interview Guide rated the management qualities "seeing the big picture" and potential for "rehire" as the best predictors of managerial success. After two years, a good "self-concept" or a "flexible attitude" was the best predictor. The ability to manage conflict was the most significant competency for predicting rehire at both six months and two years.

Olfactory sexual inhibition and the westermarck effect.

The Westermarck effect (sexual inhibition among individuals raised together) is argued to be mediated olfactorily. Various animals, including humans, distinguish among individuals by scent (significantly determined by MHC genotype), and some avoid cosocialized associates on this basis. Possible models of olfactory mechanisms in humans are evaluated. Evidence suggests aversions develop during an early sensitizing period, attach to persons as much as to their scents, and are more powerful among females than among males. Adult to child aversions may develop similarly, but more likely result from stimulus generalization. This hypothesis accords with current evidence and yields testable predictions (e.g., anosmia will prevent inhibition) that, should they be supported, will conclusively ground the Westermarck effect in a biological mechanism.

Contact-dependent hemolytic activity distinct from deforming activity of Bartonella bacilliformis.

Although Bartonella bacilliformis causes a severe anemia in humans, this study presents the first report of hemolytic activity by B. bacilliformis. The activity was not apparent in culture supernatants but was reliably detected when B. bacilliformis cells were centrifuged onto erythrocytes prior to incubation. Abrogation of hemolytic activity by proteinase K treatment suggested the hemolysin was a Bartonella protein. Even though hemolysis required relatively long incubation times, de novo protein synthesis was not required to produce the protein. A preparation containing factors released by B. bacilliformis, including deformin, a B. bacilliformis protein able to induce pits and invaginations in erythrocyte membranes, had some ability to lyse erythrocytes. However, pre-deformed erythrocytes did not lyse faster or to a greater extent than control erythrocytes after the addition of B. bacilliformis cells. Inhibition of deformation caused by B. bacilliformis cells with the erythrocyte ATPase inhibitor, vanadate, did not affect hemolytic activity. This study suggests hemolytic activity and deforming activity are attributable to different B. bacilliformis proteins.

Differential expression of translational elements by life cycle variants of Coxiella burnetii.

Coxiella burnetii replicates as distinct morphological forms, which may allow potential life cycle variants to survive the harsh environment of the phagolysosome. Monoclonal antibodies (MAbs) were compared by Western blotting for reactivity with large cell variant (LCV) and small cell variant (SCV) antigens to characterize proteins differentially expressed by C. burnetii. MAb NM7.3 reacted with a approximately 32-kDa LCV-upregulated antigen, and MAb NM183 reacted with a approximately 45-kDa LCV-specific antigen. MAb NM7.3 was used to screen a lambdaZapII C. burnetii DNA expression library, and an immunoreactive clone was identified with sequence similarity to the Escherichia coli tsf gene, which encodes elongation factor Ts (EF-Ts). Since a similar screen with MAb NM183 did not identify immunoreactive clones, an alternate strategy was devised to clone the reactive antigen based on observations of cross-reactivity with the 45-kDa elongation factor Tu (EF-Tu) protein from Chlamydia trachomatis. The highly conserved nature of EF-Tu among eubacteria allowed PCR amplification of a tuf gene fragment (encoding approximately 95% of the predicted EF-Tu open reading frame) from C. burnetii using degenerate primers. The product of the cloned tuf gene fragment reacted with MAb NM183 in Western blot analysis, confirming the identity of the 45-kDa LCV-specific antigen. Identification of two proteins differentially expressed by C. burnetii, EF-Tu and EF-Ts, both essential components of the translational machinery of the cell, supports the hypothesis that LCVs are metabolically more active than SCVs.

Selective thrombolysis of central retinal artery occlusion without long-term systemic heparinization.

BACKGROUND: A central retinal artery occlusion is a potentially blinding retinal vascular event with no effective treatment regimen available. Recently, a few reports have described improved vision in eyes with central retinal artery occlusions after selective fibrinolytic therapy followed by long-term systemic anticoagulation. Acceptance of this treatment, however, has been hampered by a paucity of confirmatory reports and its potential for producing serious hemorrhagic complications. Our report independently confirms the beneficial effects of selective thrombolysis, even with the use of only short-term, post-procedure systemic heparinization. METHODS: A case report of selective fibrinolysis of an occluded central retinal artery using urokinase infusion into the ophthalmic artery followed with only 12 h of systemic heparinization is described. RESULTS: A 65-year-old man presenting with a central retinal artery occlusion of less than 4-h duration enjoyed an improvement of vision from counting-fingers acuity to 20/20 after selective fibrinolysis with urokinase and only 12 h of systemic heparinization. No hemorrhagic or thrombotic complications occurred. CONCLUSIONS: Selective thrombolysis with urokinase followed by short-term systemic heparinization can effectively treat a central retinal artery occlusion. Whereas the authors acknowledge that a single case does not prove that short-term heparinization is better than long-term heparinization, it does show that the latter is not always required.

Plasmodium falciparum chloroquine and quinine sensitivity in asymptomatic and symptomatic children in São Tomé Island.

Plasmodium falciparum sensitivity to quinine in São Tomé was determined by in vivo and in vitro tests in 56 children with mild or cerebral malaria. Chloroquine sensitivity was assessed by in vitro tests in 105 parasitaemic asymptomatic children from the same community as the cases. The WHO standard methodology was used. No resistance to quinine was found by in vivo or in vitro tests in either group of patients or in asymptomatic children, although some degree of chloroquine resistance was found with the in vitro test. This was more common in patients than in asymptomatic children. Chloroquine resistance may be explained by the recent history of malaria in São Tomé Island, which caused an important decrease of immunity among the population and consequently the emergence of resistant strains. Implications of the use of in vivo/in vitro tests for determining the antimalarial drug policy within the primary health care system are discussed.

Multiple myeloma with hairy cell-like features.

Hairy cell leukemia (HCL) and multiple myeloma (MM) are well-described disease entities with characteristic clinical and pathologic features. We describe two patients initially treated for MM in whom atypical clinical and morphologic features subsequently developed that raised the possibility of HCL. Although the cytologic appearance and immunophenotype were not diagnostic of HCL, these cases challenge the criteria used to diagnose MM, HCL, and other recently described villous neoplasms.

Cirsoid aneurysm treatment by percutaneous injection of sodium tetradecyl sulfate.

BACKGROUND: Cirsoid aneurysms are uncommon arteriovenous fistulas of the scalp. Surgery for these lesions can be difficult; transarterial embolization is rarely curative, while embolization of the venous pouch with permanent agents usually necessitates subsequent surgical removal of the embolic material. The ideal embolic agent would be one that is safe and effective, commercially available, and would not require subsequent removal. METHODS: We treated an arteriovenous fistula of the scalp with direct puncture and injection of sodium tetradecyl sulfate, a commercially available sclerosing agent. RESULTS: Control angiography immediately following percutaneous injection of sotradecol into the fistula showed decreased flow but not complete closure of the lesion. However, within several days of the embolization, the patient's scalp pain and mass resolved. Four months after embolization, MRA demonstrated no evidence of residual or recurrent fistula. Color doppler flow imaging demonstrated only slightly decreased vascular resistance in the distal superficial temporal artery, possibly indirect evidence of persistent micro-fistulae. Twenty-three months after the procedure, the patient continued to be asymptomatic and had no palpable lesion. CONCLUSIONS: Percutaneous injection of sotradecol can be considered as one of the treatment options for arteriovenous fistula of the scalp. Further experience is needed to compare the safety and effectiveness of sotradecol with other agents currently used in the treatment of scalp arteriovenous fistulae.

A highly efficient in vitro cloning procedure for asexual erythrocytic forms of the human malaria parasite Plasmodium falciparum.

A very reliable and productive technique for cloning of Plasmodium falciparum in vitro is proposed, as demonstrated by successive limiting dilution of suspensions of asexual erythrocytic forms of the NF 54 strain. The introduction and the study of reliable clones is of extreme importance for a better understanding of the behaviour of the parasite, also in field conditions. The method is rapid, simple and efficient. The growth of the clones was individually monitored and the culture conditions were constantly adjusted during their stay in recipients of increasing size. A yield of 18/96 (18.75%) of provisional clones was obtained, while the supercloning phase resulted in 16/80 (20%) positive cultures. The probability that the latter were derived from a single progenitor is very high (99%). It was shown that three randomly selected clones (A1A9, A1B11, and A1C10) have excellent growth characteristics before and after cryopreservation, and after a longer period of culture in standard conditions.

Papaverine-induced mydriasis.

Five cases of ipsilateral pupillary dilatation that developed during local intraarterial infusion of papaverine are reported. All patients were being treated for symptomatic vasospasm secondary to subarachnoid hemorrhage. In each case, the tip of the infusion catheter was positioned in the internal carotid artery in close proximity to the ostium of the ophthalmic artery. Pupillary dilatation in all patients readily resolved after termination of the infusion.

Cloning and sequencing of Coxiella burnetii outer membrane protein gene com1.

The gene for an approximately 27-kDa outer membrane-associated, immunoreactive protein was cloned from the rickettsial pathogen Coxiella burnetii. The gene, designated com1 for Coxiella outer membrane protein 1, was expressed in Escherichia coli, presumably by its own promoter. The complete nucleotide sequence of the gene was determined. The deduced amino acid sequence of 252 residues includes a putative leader sequence. The leader sequence is recognized in and removed by E. coli on the basis of the difference in the molecular mass of the protein produced in an in vitro transcription-translation system (27.6 kDa) and that of the protein immunoprecipitated from an iodinated E. coli clone (25.7 kDa). The Com1 protein expressed in E. coli was proteinase K sensitive in nondisrupted cells and soluble in 1% Sarkosyl, suggesting a loose association with the outer membrane. While the complete predicted sequence of the Com1 protein does not show any overall similarity to those of previously described proteins, a region which includes the only two cysteines in Com1 is homologous to the catalytic site of protein disulfide oxidoreductases.

Three-dimensional time-of-flight MR angiography with a surface coil: evaluation in 12 subjects.

We compared three-dimensional time-of-flight MR angiograms obtained with head coils and then with surface coils in five patients with intracranial vascular lesions and in seven normal volunteers to determine if imaging of intracranial vascular anatomy could be improved with the use of a surface coil. Visualization of small peripheral vessels was consistently better with a surface coil than with a head coil at identical small fields of view (FOVs). The surface-coil technique allowed small-FOV imaging of peripheral vascular lesions with higher spatial resolution and signal-to-noise ratio similar to that of large-FOV head-coil images. The use of a surface coil introduced the problem of signal falloff; centrally located vessels were visualized as well or better when a standard head coil was used. We conclude that surface-coil MR angiography can serve as a useful adjunct to routine head-coil MR angiography in the evaluation of peripheral vascular abnormalities.