Constrained non-rigid registration for use in image-guided adaptive radiotherapy.

A constrained non-rigid registration (CNRR) algorithm for use in prostate image-guided adaptive radiotherapy is presented in a coherent mathematical framework. The registration algorithm is based on a global rigid transformation combined with a series of local injective non-rigid multi-resolution cubic B-spline Free Form Deformation (FFD) transformations. The control points of the FFD are used to non-rigidly constrain the transformation to the prostate, rectum, and bladder. As well, the control points are used to rigidly constrain the transformation to the estimated position of the pelvis, left femur, and right femur. The algorithm was tested with both 3D conformal radiotherapy (3DCRT) and intensity-modulated radiotherapy (IMRT) dose plan data sets. The 3DCRT dose plan set consisted of 10 fan-beam CT (FBCT) treatment-day images acquired from four different patients. The IMRT dose plan set consisted of 32 cone-beam CT (CBCT) treatment-day images acquired from 4 different patients. The CNRR was tested with different combinations of anatomical constraints and each test significantly outperformed both rigid and non-rigid registration at aligning constrained bones and critical organs. The CNRR results were used to adapt the dose plans to account for patient positioning errors as well as inter-day bone motion and intrinsic organ deformation. Each adapted dose plan improved performance by lowering radiation distribution to the rectum and bladder while increasing or maintaining radiation distribution to the prostate.

A constrained non-rigid registration algorithm for use in prostate image-guided radiotherapy.

A constrained non-rigid registration (CNRR) algorithm for use in updating prostate external beam image-guided radiotherapy treatment plans is presented in this paper. The developed algorithm is based on a multi-resolution cubic B-spline FFD transformation and has been tested and verified using 3D CT images from 10 sets of real patient data acquired from 4 different patients on different treatment days. The registration can be constrained to any combination of the prostate, rectum, bladder, pelvis, left femur, and right femur. The CNRR was tested with 5 different combinations of constraints and each test significantly outperformed both rigid and non-rigid registration at aligning constrained bones and critical organs. The CNRR was then used to update the treatment plans to account for articulated, rigid bone motion and non-rigid organ deformation. Each updated treatment plan outperformed the original treatment plan by increasing radiation dosage to the prostate and lowering radiation dosage to the rectum and bladder.

TRACKING ORGAN OVERLAP FOR A CONSTRAINED NON-RIGID REGISTRATION ALGORITHM.

This paper tracks organ (prostate, rectum, bladder) overlap in a constrained non-rigid registration (NRR) algorithm to register computed tomographic (CT) images used in external beam prostate radiotherapy. The local motion of the organs is described by a hierarchical multi-resolution FFD based on cubic B-splines. Registration is achieved by minimizing a cost function which is a combination of three functions representing the overlap of the critical organs, image similarity and smoothness of the transformation. The constrained NRR algorithm generated better registration results when compared to an unconstrained NRR algorithm.

A CONSTRAINED NON-RIGID REGISTRATION ALGORITHM FOR APPLICATION IN PROSTATE RADIOTHERAPY.

This paper presents a novel free-form deformation registration algorithm with non-rigid constraints to capture the transformation between the planning day and treatment day CT images used for external beam radiotherapy for prostate cancer. The algorithm is constrained to the predetermined motion of a segmented organ, which is described by an injective free-form deformation (FFD) based on B-splines. The end goal is for the injective transformation to be used to update the radiotherapy plan to take into account bone and soft tissue deformation. The results of the algorithm have been compared to those achieved using rigid and fully non-rigid registration. The results clearly indicate that the constrained non-rigid registration algorithm presented in this paper performed much better at capturing the motion of the constrained organ, the bladder in this case, than the rigid or fully non-rigid registration algorithms.

Detection of shared magnetic antigenic determinants on whole Moraxella bovis pili by use of antisera to cyanogen bromide-cleaved M. bovis pilus protein.

OBJECTIVE: To determine the ability of antisera against cyanogen bromide-cleaved pili from 4 strains of Moraxella bovis to react with whole or nondenatured pili. SAMPLE POPULATION: Antisera to 4 strains of M. bovis produced by New Zealand White rabbits. PROCEDURE: Pili from 4 strains of M. bovis were collected and purified. Pilus proteins (pilin) were cleaved, using cyanogen bromide. Whole pilus and cyanogen bromide-cleaved pilin were injected into rabbits. Antisera were serially diluted, reacted with 4 strains of M. bovis, and examined by immunoelectron microscopy and indirect immunofluorescence. RESULTS: Antisera to whole pili aggregated and distorted pili from homologous strains, but pili from heterologous strains were unaffected. Antisera to cleaved pilin fragments resulted in partial aggregation and thickening of homologous and heterologous pili, suggestive of heterospecific antibodies. Attachment of antibodies to pili was detected by indirect immunofluorescence, indicating a strong reaction of antisera to whole pili with homologous pili. Weak cross-reactions were evident with certain heterologous strains. In contrast, antisera to cleaved pilin fragments reacted strongly with pili from homologous and heterologous strains. CONCLUSIONS AND CLINICAL RELEVANCE: We detected shared antigenic determinants on pili from various strains of M. bovis that were not immunogenic in intact pili. These sites were immunogenic after cleavage of pilus protein with cyanogen bromide, and antisera produced to protein fragments reacted with whole pili from heterologous strains of the organism. Vaccines produced from cyanogen bromide-treated pili may induce broader immunity against infectious bovine keratoconjuctivitis than that provided by currently available vaccines.

Immunoblot analysis of cyanogen bromide-cleaved Moraxella bovis pilin reveals presence of shared antigenic determinants on pili from heterologous strains.

Moraxella bovis pilus proteins, collected and purified from four strains of M. bovis, were cleaved with cyanogen bromide. Two major fragments were produced. Antisera were produced in rabbits to the pilin protein fragments and to whole uncleaved pili from these strains. Immunoblots of whole and cyanogen bromide-cleaved pilin were reacted with the homologous and heterologous antisera to whole pili and cleaved pilin. Antisera to whole pili reacted strongly with homologous pilin. Weaker and inconsistent reactions were detected with heterologous pilin. Antisera produced to cyanogen bromide-cleaved pilin proteins reacted strongly with homologous and heterologous pilin fragments and uncleaved pilin proteins. These findings demonstrate the presence of conserved antigenic determinants on pili from heterologous strains that are non-immunogenic in the intact pilus but are immunogenic after treatment with cyanogen bromide. Cyanogen bromide-treated pilus preparation might have potential as a vaccine because antibodies are induced against heterologous strains of M. bovis, whether these cross-reactive antibodies are protective remains to be determined.

Herpes simplex-induced fulminant hepatitis in adults: a call for empiric therapy.

Herpes simplex-induced fulminant hepatitis is an infrequently reported cause of hepatitis in adults. Pregnant females and patients with impaired cellular immunity may be at increased risk, although healthy adults have been affected. The diagnosis may be underrecognized due to nonspecific presenting symptoms and lack of typical cutaneous herpes lesions. We present three cases of fatal herpes simplex fulminant hepatitis. Our review of case reports of herpes simplex hepatitis in adults demonstrates improved survival with intravenous acyclovir therapy. We believe that empiric use of acyclovir should be considered while the diagnostic evaluation of non-acetaminophen-induced fulminant hepatitis is underway. Recognition of characteristic liver function abnormalities seen with fulminant herpes simplex hepatitis include marked elevation of transaminases with AST > ALT and a mild hyperbilirubinemia (anicteric hepatitis), and they should prompt acyclovir therapy. This is especially true when there are no obvious risk factors for other forms of hepatitis.

Society for Healthcare Epidemiology of America and Infectious Diseases Society of America Joint Committee on the Prevention of Antimicrobial Resistance: guidelines for the prevention of antimicrobial resistance in hospitals.

Antimicrobial resistance results in increased morbidity, mortality, and costs of health care. Prevention of the emergence of resistance and the dissemination of resistant microorganisms will reduce these adverse effects and their attendant costs. Appropriate antimicrobial stewardship that includes optimal selection, dose, and duration of treatment, as well as control of antibiotic use, will prevent or slow the emergence of resistance among microorganisms. A comprehensively applied infection control program will interdict the dissemination of resistant strains.

Society for Healthcare Epidemiology of America and Infectious Diseases Society of America Joint Committee on the Prevention of Antimicrobial Resistance: guidelines for the prevention of antimicrobial resistance in hospitals.

Antimicrobial resistance results in increased morbidity, mortality, and costs of health care. Prevention of the emergence of resistance and the dissemination of resistant microorganisms will reduce these adverse effects and their attendant costs. Appropriate antimicrobial stewardship that includes optimal selection, dose, and duration of treatment, as well as control of antibiotic use, will prevent or slow the emergence of resistance among microorganisms. A comprehensively applied infection control program will interdict the dissemination of resistant strains.

Gastric flora in chronically mechanically ventilated patients. Relationship to upper and lower airway colonization.

The oropharynx, stomach, and trachea are all potential reservoirs for gram-negative organisms in mechanically ventilated patients. The pathogenic importance of each site in respiratory infection may differ between mechanically ventilated patients who are medically stable and the critically ill, and these differences may be important in understanding the pathogenesis of nosocomial infection. We prospectively studied seven patients requiring chronic ventilatory assistance who were otherwise medically stable to determine the pattern of gram-negative colonization of these three sites. Serial weekly oropharyngeal, gastric, and tracheal cultures were taken over a 6-mo period in our Respiratory Care Unit for chronically ventilator-dependent patients. Pseudomonas aeruginosa (PA) was present more frequently and persistently in the trachea than the oropharynx and stomach (p < 0.01) and members of the family Enterobacteriaceae (Ent. species) were also observed more commonly in the trachea than the oropharynx (p < 0.01). PA was seen in 6.7% of gastric specimens whereas Ent. species were found in 40% of gastric specimens. Six identical strains from a total of 53 gastric isolates and 128 oropharyngeal isolates were cultured coincidentally from these two sites. Coincidental isolation of 11 strains was observed in 177 tracheal isolates and 53 gastric samples. Documented transfers from stomach to oropharynx ascertained by sequential isolation occurred in one of 118 cultures and transfer from stomach to trachea occurred in three of 134 cultures.(ABSTRACT TRUNCATED AT 250 WORDS)

Preliminary findings from the survey about AIDS for seventh and eighth graders (SASEG).

Four hundred and twelve seventh- and eighth grade students from a predominantly white, suburban, middle-class school were surveyed regarding their knowledge and attitudes about AIDS. The Survey about AIDS for Seventh and Eighth Graders (SASEG) utilized for the study is a 56-item, self-administered questionnaire that includes 26 multiple-choice knowledge items, 20 Likert-type attitude items, and 10 demographic/experiential items. Overall, students were judged to possess reasonably high knowledge levels and generally favorable attitudes regarding AIDS. However, there were several areas of misinformation and unfavorable attitudinal responses. A low positive relationship was found between knowledge and attitudes. Higher levels of knowledge and more favorable attitudes were associated with being female, being older, and having discussed AIDS with one's parents. Higher levels of knowledge were also associated with having had previous AIDS instruction and with not knowing someone with AIDS. These findings support the need for AIDS education in the pre-high school setting.

Hansenula anomala: a new fungal pathogen. Two case reports and a review of the literature.

Fungal infections are characteristic of severely immunocompromised patients. Noncandidal yeasts represent a growing proportion of such infections. Risk factors for developing fungal infections include the use and abuse of central venous catheters. Two patients with gynecologic malignant neoplasms became fungemic with Hansenula anomala, a yeast of the Ascomycetes class, after insertion of central venous catheters. Frequent catheter manipulation and prolonged use favored the development of fungemia in both patients. A review of the literature revealed 19 additional cases over the course of four decades, all in hosts with underlying diseases. Thirteen of these cases have been described in the last 18 months, suggesting either increased recognition or increased frequency of infection with this organism. All tested isolates have been susceptible to amphotericin B. Patients have generally responded to catheter withdrawal and amphotericin B administration. Hansenula anomala is an opportunistic pathogen, whose clinical behavior resembles that of Candida species.

Management of infection in myelosuppressed patients: clinical trials and common sense.

In the past fifteen years, enormous research effort has been expended in pursuit of the "ideal" approach to the management of infection in the myelosuppressed, i.e., granulocytopenic, patient. In the welter of clinical trials, some "commonsense" fundamentals have been lost or submerged, while other ideas seem to have become "modern myths." Among those commonsense approaches that should not be forgotten are the following: Granulocytopenia often precludes even the most skilled observer from assessing whether a febrile patient is truly infected. The epidemiology of infection at the local institution should be the principal determinant of the empiric antibiotic regimen in use. There is no ideal empiric antibiotic regimen. In particular, there is no absolute necessity for antipseudomonal penicillins, for aminoglycosides or for combinations of antibiotics. Some modern myths that seem to have been widely accepted without adequate data are: Antibiotic "synergism" is an essential prerequisite to a successful outcome of infection in the granulocytopenic patient. In the febrile granulocytopenic patient who responds to treatment, antibiotics should be continued until the granulocytopenia resolves. In the febrile granulocytopenic patient who does not respond to treatment, all such patients should receive amphotericin B for empiric antifungal treatment. These and other modern myths and aspects of common sense will be discussed in light of recent clinical trials.

The acquired immune deficiency syndrome (AIDS): current status and implications for respiratory care practitioners.

The acquired immune deficiency syndrome (AIDS) has affected more than 2,600 persons since 1981, with the number of reported cases rising exponentially. The disease is characterized by a deficiency in the cell-mediated immune system, which allows entrance to a host of opportunistic infections as well as tumors. The most common infection associated with AIDS is Pneumocystis carinii pneumonia, a previously uncommon infection of immunocompromised hosts. The most common neoplasm associated with AIDS is an otherwise rare skin tumor, Kaposi's sarcoma. AIDS is most often seen in homosexuals and intravenous-drug abusers, but the spectrum of the disease is widening and now includes other high-risk groups. The pulmonary manifestations of AIDS range from a nonproductive cough to acute respiratory failure. Once hospitalized, the AIDS patient may require several diagnostic and therapeutic services from respiratory care personnel. We review the epidemiology of this new syndrome, provide the basic framework for an understanding of the immunologic dysfunction in AIDS victims, review the clinical manifestations, and discuss the implications of the communicability of AIDS for the respiratory care practitioner.

Recent developments in nosocomial infections and their control.

Hospital epidemiology has advanced as a discipline largely because of contributions from government and certifying agencies, and from recognition that nosocomial infections are unique and require specialized attention. A modern infection control program should consist of surveillance, outbreak investigation, consultative services, education, and research activities. Guidance for program development may be obtained from an institution such as the Centers for Disease Control. This agency has provided standardized definitions as well as guidelines for care. An effective infection control program can improve the understanding and prevention of hospital-acquired infections.