Review: Using physiologically based models to predict population responses to phytochemicals by wild vertebrate herbivores.

To understand how foraging decisions impact individual fitness of herbivores, nutritional ecologists must consider the complex in vivo dynamics of nutrient-nutrient interactions and nutrient-toxin interactions associated with foraging. Mathematical modeling has long been used to make foraging predictions (e.g. optimal foraging theory) but has largely been restricted to a single currency (e.g. energy) or using simple indices of nutrition (e.g. fecal nitrogen) without full consideration of physiologically based interactions among numerous co-ingested phytochemicals. Here, we describe a physiologically based model (PBM) that provides a mechanistic link between foraging decisions and demographic consequences. Including physiological mechanisms of absorption, digestion and metabolism of phytochemicals in PBMs allows us to estimate concentrations of ingested and interacting phytochemicals in the body. Estimated phytochemical concentrations more accurately link intake of phytochemicals to changes in individual fitness than measures of intake alone. Further, we illustrate how estimated physiological parameters can be integrated with the geometric framework of nutrition and into integral projection models and agent-based models to predict fitness and population responses of vertebrate herbivores to ingested phytochemicals. The PBMs will improve our ability to understand the foraging decisions of vertebrate herbivores and consequences of those decisions and may help identify key physiological mechanisms that underlie diet-based ecological adaptations.

The therapeutic potential of immune cross-talk in leishmaniasis.

Veterans of infection, Leishmania parasites have been plaguing mammals for centuries, causing a morbidity toll second only to that of malaria as the most devastating protozoan parasitic disease in the world. Cutaneous leishmaniasis (CL) is, by far, the most prevalent form of the disease, with symptoms ranging from a single self-healing lesion to chronic metastatic leishmaniasis (ML). In an increasingly immunocompromised population, complicated CL is becoming a more likely outcome, characterized by severely inflamed, destructive lesions that are often refractory to current treatment. This is perhaps because our ageing arsenal of variably effective antileishmanial drugs may be directly or indirectly immunomodulatory and may thus have variable effects in each type and stage of CL. Indeed, widely differing immune biases are created by the various species of Leishmania, and these immunological watersheds are further shifted by extrinsic disturbances in immune homeostasis. For example, we recently showed that a naturally occurring RNA virus (Leishmania RNA virus (LRV)) within some Leishmania parasites creates hyperinflammatory cross-talk, which can predispose to ML: a case of immunological misfire that may require a different approach to immunotherapy, whereby treatments are tailored to underlying immune biases. Understanding the intersecting immune pathways of leishmaniasis and its co-infections will enable us to identify new drug targets, and thereby design therapeutic strategies that work by untangling the immunological cross-wires of pathogenic cross-talk.

Benign mucinous metaplasia of the genital mucosa: histomorphological and immunohistochemical features and criteria for differentiation from extramammary Paget disease.

BACKGROUND: Benign mucinous metaplasia of the genitalia (BMM) is a rare condition typified by cells with foamy mucinous cytoplasm. Differential diagnoses include extramammary Paget disease (PD) and human papillomavirus (HPV)-induced vulval intraepithelial neoplasia (VIN) with mucinous differentiation. OBJECTIVES: To characterize histopathological and immunohistochemical features of BMM and to forge criteria for differentiation from PD and VIN with mucinous differentiation. METHODS: Eight biopsy specimens of BMM were stained with haematoxylin and eosin, periodic acid-Schiff and alcian blue, and for cytokeratin (CK) 7, CK10, CK14, CK20, carcinoembryonic antigen (CEA), epithelial membrane antigen (EMA), S100, gross cystic disease fluid protein-15 (GCDFP-15), lysozyme and Ki67 and compared with PD. Polymerase chain reaction was performed in order to identify HPV-specific DNA. RESULTS: BMM showed mucin deposition in superficial epithelial layers ranging from numerous large goblet cells to subtle deposits. The epithelium often showed polygonal (squamoid) or cuboidal differentiation while columnar differentiation was an inconsistent feature. A band-like inflammatory infiltrate was consistently present. Metaplastic epithelium consistently expressed CK7, CEA and EMA either in the entire epithelium or in a superficial band, while CK14, CK10, GCDFP-15 and lysozyme were largely not expressed, and staining for CK20 and S100 was negative. Comparison with PD demonstrated similar staining characteristics, but in a scattered pattern of mucinous cells within preserved squamous epithelium and not in a band-like pattern as in BMM. Nuclear pleomorphism and Ki67-positive mucinous cells in superficial epithelial layers were seen only in PD; GCDFP-15 and/or lysozyme were expressed in the majority of cases of PD. No evidence of HPV-specific DNA was found in BMM. CONCLUSIONS: The spectrum of changes in BMM is distinctive, and BMM can be differentiated with surety from both PD and VIN with mucinous differentiation.

[The treatment of malignant tumors on venous leg ulcers. Case presentation and literature review]. / Therapie maligner Tumoren auf venösen Beinulzera. Kasuistik und Literaturübersicht.

Malignant changes in persistent venous leg ulcers are a grave complication of chronic impaired wound healing. In our case, a venous leg ulcer had persisted on the right calf for 30 years. Exophytic tumors in the ulcer with frequent bleeding prompted biopsies. A squamous cell carcinoma was found, but only in the second biopsy. The surgical procedure was planned so that in a single session both the tumor and the underlying causes of the chronic venous insufficiency in the leg could be treated appropriately. Extirpation of the enlarged lymph nodes in the groin was combined with crossectomy and removal of the long saphenous vein, followed by circular radial excision of the ulcer scar fascia (fasciotomy). The excised tissue was examined histologically. Muscle biopsies were taken from the site of suspicious adhesions of the fascia to the calf muscle. The large, circular defects on the lower leg were covered with the appropriate dressing to condition the wound bed. After three weeks the well-granulated area was covered with meshed split skin grafts. During the operation and in the post-operative phase, machine-assisted and manual decongestion was performed, an established therapy for lymphedema, chronic venous insufficiency and chronic venous ulcers.

Trichophyton rubrum-induced inflammatory tinea capitis in a 63-year-old man.

Tinea capitis caused by Trichophyton rubrum is a rare event worldwide. We report on an elderly otherwise healthy man with inflammatory fungal disease of the scalp caused by this pathogen. He had no signs of concomitant mycosis of the skin and nails and no underlying immunosuppressive disease. The fungal infection primarily had been misdiagnosed in terms of a pyoderma. Failure of antibiotic treatment, a positive mycological study and molecular diagnostics eventually led to the correct diagnosis. After systemic and local administration of terbinafine the lesion improved totally.

Screening of males for Chlamydia trachomatis and Neisseria gonorrhoeae infections at STD clinics in three US cities -- Indianapolis, New Orleans, Seattle.

We assessed prevalence and risk factor data for men routinely screened for Chlamydia trachomatis and Neisseria gonorrhoeae in STD clinics in four US cities from May 1995-March 1999. Data were analysed separately for 'test-visits' (self-reported symptoms, clinical signs or sexual contact to an STD) and 'screen-visits' (STD screen only) for 32,595 men with 45,390 visits. Among test-visits in Seattle, Indianapolis and New Orleans, 8.7% (807/9285), 15.3% (1305/8519), and 10.1% (1551/15,296) of men were positive for C. trachomatis, and 10.2% (773/7543), 24.9% (2108/8478), and 30.4% (4746/ 15,629) for N. gonorrhoeae. Among screen-visits, 2.1% (88/4103), 7.3% (130/1790), and 5.6% (292/5183) of men were positive for C. trachomatis, and 1.8% (46/2576), 1.7% (31/ 1786), and 5.2% (274/5235) for N. gonorrhoeae. Positivity for screen-visits was particularly high among young men (15-24 years), and those reporting > 1 sex partner in the past 60 days. Substantial variation among sites in positivity warrants local determination of prevalence and risk factors to inform screening strategies.

Relationship between home food-handling practices and sporadic salmonellosis in adults in Louisiana, United States.

Salmonellosis is the leading cause of death caused by foodborne bacterial pathogens in the United States. Approximately 90% of salmonella infections are sporadic, but most of what is known about salmonellosis has come from outbreak investigations. We studied the risk for sporadic salmonellosis among 115 persons aged > or = 15 years reported to the Louisiana Office of Public Health during May 1998-April 1999, compared with 115 age-matched controls. Significantly more case-patients than controls had chronic underlying medical conditions [adjusted odds ratio (aOR) = 4.3; 95% confidence interval (CI) = 2.2-8.7]. Although reported consumption of specific food items likely to contain salmonella was not associated with illness, inconsistent handwashing between preparation of meat and non-meat items was associated with illness (aOR = 8.3; CI = 1.1-61.8). Enhanced measures to provide a consistently safe food supply and promote safer food preparation in households will depend on prevention of sporadic salmonellosis.

Functional results after anterior cruciate ligament reconstruction using the patellar ligament bone-tendon-bone technique.

This study evaluates the outcome after surgical repair of the cruciate ligament in 129 patients (physical examination plus questionnaire) and another 49 patients (questionnaire only) after a mean interval of 3.2 years. A modified Lysholm score and the OAK score together with KT 1000 arthrometry were used. Ninety-five percent of patients evaluated the overall result as 'excellent' or 'good'. The overall OAK objective score was good or excellent in 81%. Elongation as measured by KT 1000 arthrometry was 1.0 mm (67 N) and 1.2 mm (90 N) on average compared with the contralateral knee.

Initially unrecognized distribution of a commercially cooked meat product contaminated over several months with Salmonella serotype Infantis.

An outbreak of salmonellosis occurred among 63 wedding participants. The outbreak was investigated through cohort, laboratory, and environmental studies. Consumption of rice-dressing made from a commercially cooked, meat-based, rice-dressing mix was strongly associated with illness. Nineteen patient isolates, six company/grocery store isolates cultured from the rice-dressing mix, and one environmental isolate from a pump in the production line were of an identical outbreak strain of Salmonella Infantis characterized by pulsed-field gel electrophoresis. In the production line, cooked rice-dressing mix tested negative for S. Infantis before and positive after contact with the contaminated pump. The dressing-mix had an estimated 200 colony-forming units of salmonella per gram of product, and > 180,000 pounds were distributed in 9 states for > or = 2 months before contamination was recognized. Food manufacturers should be required to use systematic, hazard analysis critical control point risk management practices for all processed meat products, validated by periodic microbiologic monitoring of the end product.

Usefulness of partner notification for syphilis control.

BACKGROUND AND OBJECTIVES: In the United States, the recent syphilis epidemic has been followed by the lowest rates in 40 years. Syphilis control in the United States traditionally emphasizes partner notification; however, its role in elimination efforts remains undefined. GOAL OF THE STUDY: To describe and compare outcome measures of partner notification during and after the epidemic. STUDY DESIGN: Descriptive analysis of data obtained from interview records of patients with early syphilis in Louisiana during 1993 through 1996. RESULTS: Of 12,927 patients with early syphilis, 3,245 (25%) were identified through partner notification. A total of 7,120 (55%) patients named at least one infected contact. Patients named a mean of 2.3 contacts, resulting in 29,248 named contacts; of these, 22,825 (78%) were examined. A total of 9,374 (41%) of examined contacts were infected, including 18% who were newly identified as infected. No substantial differences were found between epidemic and postepidemic years. CONCLUSION: Partner notification is successful in identifying and treating a large number of infected persons. However, complementary strategies will be needed to eliminate syphilis.

Analysis of Gasolines by FT-IR Spectroscopy.

An experimental and computational protocol was established for the simultaneous determination of several key gasoline properties from a single Fourier transform infrared (FT-IR) spectrum. The study has shown that midband FT-IR spectroscopy combined with multivariate calibration analysis is a versatile, efficient, and accurate technique for the simultaneous estimation of key gasoline properties within about 1 min with less than 2 mL of sample. The FT-IR-derived values of gasoline properties include research and motor octane numbers, aromatic, olefinic, and saturated hydrocarbon content, benzene content, and concentrations of ethanol, methyl tert-butyl ether, and total oxygen. Concentrations of other oxygenated compounds are expected to be equally predictable. However, since these oxygen-containing species have not been adequately represented among the currently commercially available gasoline samples, their calibration may only be achieved using laboratory fuel blends. Midrange boiling point data may also be estimated. Fuel properties determined by minor concentrations of fuel components, e.g., flash point, sulfur content, etc., may not be modeled because the corresponding FT-IR signals are below detection limits of presented experimental protocol. The precision of this procedure was shown to be comparable to reproducibility of the standard laboratory analyses used for direct measurement of specific fuel properties, with squared correlation coefficient (R(2)) ranging from 0.94 to 0.99 between the two sets of measurements. This new methodology could increase the corresponding output of the petroleum laboratories by a factor of over 200 to 1 while maintaining data integrity and minimizing sample requirements, environmental hazards, and cost.

[Intracerebral hemorrhage and multiple brain abscesses caused by Bacillus cereus within the scope of acute lymphatic leukemia]. / Intrazerebrale Blutung und multiple Hirnabszesse durch Bacillus cereus im Rahmen einer akuten lymphatischen Leukämie.

Multiple hematogenic brain abscesses in immunosuppression are occasionally caused by rare and primary apathogenic causative agents. We report a first case of an isolated CNS infection by Bacillus cereus, which led to death from multiple brain abscesses and an intracerebral hemorrhage, probably caused by the infection, within 4 days. The underlying disease leading to immunosuppression was acute lymphatic leukemia in complete remission. In spite of antibiotic therapy the chemotherapy-induced neutropenia enabled unhindered spreading of the necrotizing infection, which was verified by histological analysis. The production of potent toxins such as hemolysin and cerelolysin by B. cereus leads to rapid and fulminant tissue destruction usually involving the walls of blood vessels.

Detection of microplatelet formation using an electroimpedance cell counter.

Changes in the platelet size distribution curves during the process of ADP-induced aggregation were observed using a particle distribution analyzer (PDA) based on electronic impedance. The maximum primary aggregation was seen at a final ADP concentration of 3 microM. After stimulation, the platelet distribution curve changed rapidly from a log normal curve to a curve skewed to the left. When the changes were evaluated at 1 min after the addition of ADP, the peak height was increased, and the median and total volume were decreased significantly. These findings indicate that microplatelets are formed by membrane stimulation and this formation can be monitored with the use of this automated instrument.

Prehospital thrombolysis: beneficial effects of very early treatment on infarct size and left ventricular function.

OBJECTIVES: The purpose of this study was to compare the effects of very early (< or = 1.5 h after symptom onset) and later (> 1.5 up to 4 h) thrombolytic therapy on infarct size, left ventricular function and early mortality in patients with acute myocardial infarction. To start thrombolysis at the earliest possible moment, it was performed in the prehospital setting. A cutoff time of 1.5 h was prospectively stipulated. BACKGROUND: Shortening of ischemic time is crucial within the 1st 2 h. Prehospital thrombolysis can reduce time to treatment and enables very early initiation of therapy for many patients. METHODS: One hundred seventy patients received 30 mg of anistreplase up to 4 h from symptom onset by a mobile intensive care unit physician. Infarct size was measured from cumulative release of alpha-hydroxybutyrate dehydrogenase, and left ventricular function was assessed by contrast angiograms 10 days after the infarction. RESULTS: The decision to treat on scene was correct in 98% of patients. There were no bleeding complications or deaths outside the hospital setting. In 28 patients (17%) the ischemic process was interrupted. Findings with thrombolytic therapy initiated < or = 1.5 (96 patients) versus > 1.5 h (74 patients) were the following: initial extent of epicardial injury, 1.6 +/- 0.9 versus 1.4 +/- 0.7 mV, p = NS; infarct size by cardiac enzyme release 646 +/- 634 versus 886 +/- 712 IU/liter, p < 0.05; ejection fraction 57 +/- 14% versus 51 +/- 13%, p < 0.05; regional dyssynergic area 24 +/- 22 versus 33 +/- 24 U, p < 0.05; 21-day mortality 1 of 96 versus 5 of 74 patients (1% vs. 7%, p < 0.05). CONCLUSIONS: The data suggest that in evolving myocardial infarction up to 4 h in duration, the start of thrombolytic therapy at < or = 1.5 h compared with > 1.5 h limits infarct size, preserves left ventricular function and may save lives.

Failure of polymyxin B nonapeptide to augment bactericidal activities of novobiocin, rifampin, and of defibrinated human blood against Serratia marcescens.

Polymyxin B (PB) and polymyxin B nonapeptide (PBNP), when combined with rifampin or novobiocin, but not vancomycin, yielded additive inhibitory effects against test strains of Serratia marcescens of three varieties: those that produced cocarde growths around PB disks (coc+); those that grew adjacent to PB disks (coc-, 6); and those that yielded clear inhibition zones around PB disks (coc-, clear). However, time kill curve experiments disclosed that only the combination of rifampin + PB exerted a potent bactericidal effect against coc+ strains of S. marcescens; rifampin + PBNP and novobiocin + PB or PBNP merely effected transient decreases of colony counts. Assays involving 50% (v/v) of fresh defibrinated human blood + PB or PBNP revealed that only PB clearly augmented the antibacterial activity of blood against coc+, and less so against coc- test strains of S. marcescens.

Staphylococcus haemolyticus: cocarde growth around imipenem disks.

Twelve multiple-drug-resistant isolates of coagulase-negative staphylococci from diverse clinical sources, which had yielded cocarde growths (double zones of inhibition) around 10 micrograms imipenem disks, were identified as Staphylococcus haemolyticus. This was the only staphylococcal species which exhibited this unusual phenotypic trait at our institution during a 7-month observation period.

In vitro activity of three fluoroquinolones against enterococci and Pseudomonas aeruginosa: modified categorization system for discrepant broth dilution and agar disk diffusion test results.

The fluoroquinolones ciprofloxacin, norfloxacin, and ofloxacin were examined in vitro against 103 enterococcal isolates and 138 isolates of Pseudomonas aeruginosa, in an attempt to determine which respective proposed interpretive criteria (minimal inhibitory concentration (MIC) versus diameter of agar disk diffusion inhibition zones) correlated best, i.e., resulted in fewer discrepant results. A previously proposed system for grouping discrepant results (very major, major, and minor discrepancies) of Barry and co-workers was modified to comprise 6 categories (very major, major, minor, slight, minimal, and negligible); this expanded system rendered the encountered discrepant in vitro test results more transparent. Overall, the currently employed interpretive criteria for norfloxacin (MICs versus 10-micrograms disks) resulted in fewer discrepancies with the above two groups of bacterial isolates than those proposed for ciprofloxacin and ofloxacin (MICs versus 5-micrograms disks, respectively).