Mucosal tolerance of the hookworm Ancylostoma caninum in the gut of naturally infected wild dogs.

Ancylostoma caninum is a very pathogenic hookworm that locates in the small intestine of the dog and other canid species. The mucosal response of wild dogs naturally infected with A. caninum was investigated in this study. In spite of diffuse infiltrations of the mucosa with CD3+ , CD4+ , CD8+ , CD11c+ , CD21+ or MHC class II antigen cells, no focal infiltrations with any of these cell phenotypes were observed around the buccal capsule or the body of the feeding worms. Very few or no apoptotic cells could be detected around the worms fixed into the mucosa but they were detected on the tip of villi and in the superficial layer of cellular debris and proteinaceous exudate that covers the mucosa. Muc5AC, a mucine associated with expulsion of gut worms (Trichuris muris) was expressed extremely weakly or was not expressed at all in the intestine of the wild dogs infected with A. caninum. Our data show that individual specimens of A. caninum can reside for some time in the mucosa of the gut of dogs undetected and most likely unaffected by the effectors of the local immune response.

Acute inflammation with induction of anaphylatoxin C5a and terminal complement complex C5b-9 associated with multiple intra-articular injections of hylan G-F 20: a case report.

OBJECTIVE: The purpose of this case report was to investigate local immune mechanisms present during an acute inflammatory flare initiated by viscosupplementation with hylan G-F 20 in a patient with osteoarthritis (OA) and past meniscectomy. EXPERIMENTAL DESIGN: A patient with a history of bilateral OA and partial left knee meniscectomy, who had received three injections of hylan G-F 20, was diagnosed with an acute flare reaction in the left knee. Her chart was evaluated for clinical, radiological, and laboratory findings and for clinical follow-up. Histopathological synovial examination and real-time polymerase chain reaction (RT-PCR) for genes with major roles in local inflammation and enzyme-linked immunosorbent assays (ELISAs) for markers of complement activation and cytokines were performed. To study the impact of the inflammatory and immune features we compared the case patient with groups of three representative OA and three rheumatoid arthritis (RA) patients. RESULTS: The patient exhibited evidence of highly increased acute phase reactant C-reactive protein (CRP) in the blood. The pathological examination of the synovial membrane identified abundant fibrinous exudate with numerous particles of hyaluronan surrounded by a dense infiltrate of neutrophils and eosinophils. The synovium had moderate hypertrophy and sclerosis as well as an inflammatory infiltrate predominantly composed of T lymphocytes and macrophages with scattered perivascular eosinophils and neutrophils. Immunoperoxidase staining identified numerous deposits of C5b-9 in the fibrinous exudates and the synovial membrane of the patient. Similar findings were observed in the RA patients, whereas deposits were rare in OA synovial samples. In addition, both anaphylatoxin C5a and the terminal complement complex C5b-9 were present at high levels, comparable to those in RA patients. The levels of mRNA for interleukin-1 beta (IL-1ß), IL-6, and the neutrophil marker myeloperoxidase (MPO) were markedly increased compared to those in the RA and OA patients. CONCLUSIONS: This present study is indicative of a pseudo-septic acute inflammatory reaction in response to local accumulation of hylan G-F 20 with the activation of complement and local invasion of pro-inflammatory cells.

Complete genome sequence of the methanogenic archaeon, Methanococcus jannaschii.

The complete 1.66-megabase pair genome sequence of an autotrophic archaeon, Methanococcus jannaschii, and its 58- and 16-kilobase pair extrachromosomal elements have been determined by whole-genome random sequencing. A total of 1738 predicted protein-coding genes were identified; however, only a minority of these (38 percent) could be assigned a putative cellular role with high confidence. Although the majority of genes related to energy production, cell division, and metabolism in M. jannaschii are most similar to those found in Bacteria, most of the genes involved in transcription, translation, and replication in M. jannaschii are more similar to those found in Eukaryotes.

Carbohydrate binding modules enhance cellulose enzymatic hydrolysis by increasing access of cellulases to the substrate.

Plant biomass is a low-cost and abundant source of carbohydrates for production of fuels, "green" chemicals and materials. Currently, biochemical conversion of the biomass into sugars via enzymatic hydrolysis is the most viable technology. Here, the role of carbohydrate binding modules (CBMs) in the disruption of insoluble polysaccharide structures and their capacity to enhance cellulase-promoted lignocellulosic biomass hydrolysis was investigated. We show that CBM addition promotes generation of additional reducing ends in the insoluble substrate by cellulases. On the contrary, bovine serum albumin (BSA), widely used in prevention of a non-specific protein binding, causes an increase in soluble reducing-end production, when applied jointly with cellulases. We demonstrate that binding of CBMs to cellulose is non-homogeneous, irreversible and leads to its amorphisation. Our results also reveal effects of CBM-promoted amorphogenesis on cellulose hydrolysis by cellulases.

Befriending patients with medication-resistant schizophrenia: can psychotic symptoms predict treatment response?

OBJECTIVES: Supportive interventions are used in schizophrenia, but little research has been conducted into whether any baseline variable predicts treatment response. The aim of this study was to establish if baseline delusions or hallucinations are associated with changes in overall symptoms in patients who received a befriending intervention. DESIGN: The sample consisted of 44 patients with schizophrenia. These patients comprised the befriending arm of a multicentre randomized controlled trial which compared the efficacy of using CBT against befriending as an adjunct to routine care for patients with medication-resistant schizophrenia. METHODS: Scores for auditory hallucinations and delusions relating to persecution or control were entered into two regression models. The dependent variables were change in overall symptoms (1) between baseline and end of the intervention, and (2) between baseline and 9 months post-intervention. RESULTS: Baseline delusions predicted a good response and auditory hallucinations predicted a poor response at 9 months. CONCLUSIONS: Baseline psychotic symptoms strongly predicted outcome in this sample. The finding that hallucinations predicted a poor outcome is consistent with previous research. These results may help to determine which patients would benefit from supportive interventions.

On the subtle tuneability of cellulose hydrogels: implications for binding of biomolecules demonstrated for CBM 1.

Cellulose-based hydrogel materials prepared by regeneration from cellulose solutions in ionic liquids, or ionic liquid containing solvent mixtures (organic electrolyte solutions), are becoming widely used in a range of applications from tissue scaffolds to membrane ionic diodes. In all such applications knowledge of the nature of the hydrogel with regards to porosity (pore size and tortuosity) and material structure and surface properties (crystallinity and hydrophobicity) is critical. Here we report significant changes in hydrogel properties, based on the choice of cellulose raw material (α- or bacterial cellulose - with differing degree of polymerization) and regeneration solvent (methanol or water). Focus is on bioaffinity applications, but the findings have wide ramifications, including in biomedical applications and cellulose saccharification. Specifically, we report that the choice of cellulose and regeneration solvent influences the surface area accessible to a family 1 carbohydrate-binding module (CBM), CBM affinity for the cellulose material, and rate of migration through the hydrogel. By regenerating bacterial cellulose in water, a maximum accessible surface area of 33 m2 g-1 was achieved. However, the highest CBM migration rate, 1.76 µm2 min-1, was attained by regenerating α-cellulose in methanol, which also resulted in the maximum affinity of the biomolecule for the material. Thus, it is clear that if regenerated cellulose hydrogels are to be used as support materials in bioaffinity (or other) applications, a balance between accessible surface area and affinity, or migration rate, must be achieved.

A randomized controlled trial of cognitive-behavioral therapy for persistent symptoms in schizophrenia resistant to medication.

BACKGROUND: Research evidence supports the efficacy of cognitive-behavioral therapy in the treatment of drug-refractory positive symptoms of schizophrenia. Although the cumulative evidence is strong, early controlled trials showed methodological limitations. METHODS: A randomized controlled design was used to compare the efficacy of manualized cognitive-behavioral therapy developed particularly for schizophrenia with that of a nonspecific befriending control intervention. Both interventions were delivered by 2 experienced nurses who received regular supervision. Patients were assessed by blind raters at baseline, after treatment (lasting up to 9 months), and at a 9-month follow-up evaluation. Patients continued to receive routine care throughout the study. An assessor blind to the patients' treatment groups rated the technical quality of audiotaped sessions chosen at random. Analysis was by intention to treat. RESULTS: Ninety patients received a mean of 19 individual treatment sessions over 9 months, with no significant between-group differences in treatment duration. Both interventions resulted in significant reductions in positive and negative symptoms and depression. At the 9-month follow-up evaluation, patients who had received cognitive therapy continued to improve, while those in the befriending group did not. These results were not attributable to changes in prescribed medication. CONCLUSION: Cognitive-behavioral therapy is effective in treating negative as well as positive symptoms in schizophrenia resistant to standard antipsychotic drugs, with its efficacy sustained over 9 months of follow-up.

Aplastic anemia associated with type B viral hepatitis.

Aplastic anemia is a recognized complication of viral hepatitis, but, to our knowledge, no cases associated with type B hepatitis have been described. We report the case of a patient who developed severe aplastic anemia very early in the course of infection with hepatitis B virus.

Acute leukemia following prolonged cytotoxic agent therapy.

1. Nine patients in whom acute non-lymphoblastic leukemia (ANLL) developed following prolonged alkylating agent therapy are described. Five of the patients received no radiotherapy. The conditions treated were: Hodgkin's disease (four patients), primary amyloidosis, primary macroglobulinemia, malignant lymphoma, multiple myeloma, and carcinoma of the tonsil. 2. Prior to the advent of chemotherapy, this complication was not observed in large series of patients with lymphoproliferative disorders and multiple myeloma. However, the medical literature now contains at least 125 other detailed reports of ANLL developing after prolonged cytotoxic agent therapy. 3. Multiple myeloma and Hodgkin's disease, both of which commonly have good responses to chemotherapy, predominate as the underlying diseases. However, 35% of the case reports involve patients with other illnesses, including 12 patients who did not have neoplasms. 4. More than half of the patients developing ANLL have received chemotherapy alone without radiotherapy. 5. At least half of the patients developing ANLL experienced long periods of significant cytopenia during therapy, often with documentation of bone marrow dysplasia. 6. The wide variety of drugs associated with this complication suggests that any cytotoxic agent may be leukemogenic. However, alkylating agents overwhelmingly predominate as the class of compounds which are most often associated with terminal ANLL. 7. The vast majority of patients reported in the literature with ANLL complicating underlying malignancies have received cytotoxic drugs for prolonged periods (median 3 1/2 years) and leukemia developed most commonly 3 to 5 years after the diagnosis of the underlying disease. Most of these patients benefited from therapy and survived longer (median 5 years) than historical control of untreated patients. 8. The leukemogenic potential in man of prolonged cytotoxic agents therapy, especially with alkylating agents, seems to be well established. This evidence admonishes against the prolonged use of these drugs in non-fatal disorders. 9. More accurate assessment of risk: benefit ratios awaits the results of prospective controlled studies. The results of these studies could also lead to significant modifications in recommendations for long-term maintenance therapy with cytotoxic agents.

Recent advances in solventless organic reactions: towards benign synthesis with remarkable versatility.

A paradigm shift away from using solvents in organic synthesis as solventless reactions can lead to improved outcomes, and more benign synthetic procedures, in for example aldol condensation reactions, sequential aldol and Michael addition reactions en route to Kröhnke type pyridines, reactions leading to 3-carboxycoumarins, benzylidenes, 4-aryl-1,4-dihydropyridines and 2-aryl-1,2,3,4-tetrahydroquinazolines, and oligomerisation reactions for the synthesis of cavitands; kinetic considerations for the reaction of two solids can only be explained if a eutectic melt is formed during the reaction.

Relationships between fertility, peak milk yields and lactational persistency in dairy cows.

Peak milk yield, lactational persistency and conception rates were studied using 5928 lactation records of high milk-producing cows at three California dairies. Log-linear analysis was used to study relationships between peak milk yield, lactational persistency, dairy of origin, lactation number and conception rates in 3850 completed lactations. Cows with peak milk yields greater than the median (38.2 kg milk per day) were less likely to have conceived in one or two breedings than cows with peak milk yields lower than or equal to the median. Cows with a higher than median (0.755) lactational persistency were less likely to have conceived in one or two breedings than cows with a lactational persistency lower than or equal to the median. Dairy of origin had a significant effect on the probability of conceiving in one or two breedings. Cows in the first lactation were more likely than those in subsequent lactations to conceive in one or two breedings. This retrospective study demonstrated that subfertility is associated with high peak lactational yields in high milk-producing California cows.

Violence as a public health emergency.

Violence threatens or denies not only the health of those who are directly affected but diminishes the whole human process. Neither the violent acts themselves, nor the repercussions of these tragedies, are limited to one geographic or social setting, and it is not just the frequency of violent actions that threatens the health of the nation. It is the ripple effect that occurs from each of these incidents that affects everyone. This article discusses the problem of national violence in the United States and examines preventive programs.

Ophthalmologic procedures.

Step-by-step instructions for the most common and difficult ophthalmologic procedures that are performed in an emergency department. Foreign body removal, including rust rings, is explained with an emphasis on limiting further injury to the corneal epithelium and stroma. Patching, irrigation, contact lens removal and corneal culture techniques are explained. Three methods of assessing intraocular pressure are described.

QT interval prolongation.

The QT interval is a function of ventricular repolarization time and is measured from the onset of the QRS complex to the end of the T wave. The length of this interval is inversely related to heart rate. A prolonged QT interval is most often secondary to the use of Type I antidysrhythmic medications (quinidine, procainamide). It is also associated with phenothiazines, organophosphates, hypocalcemia, liquid protein diets and the congenital long QT syndromes. QT prolongation is associated with a variety of ventricular dysrhythmias, most characteristically Torsades des pointes. Treatment consists of correction of the underlying metabolic disorder or discontinuation of the offending medication.

Actinomyces hordeovulneris, a canine pathogen that produces L-phase variants spontaneously with coincident calcium deposition.

The spontaneous production of cell-wall-deficient filaments and protoplasts by a strain of Actinomyces hordeovulneris (UCD 81-332-9) in 10% sucrose L-form media is reported. Multiple mineral deposits were present within the variants at 48 hours. Electron microscopy revealed that these deposits were amorphous, dense, and at the inner face of the cytoplasmic membrane in wall-less protoplasts and also in filaments which had a thin wall of 10 nm. These cell-wall-deficient variants produced L-form colonies when cultured for an additional 48 hours on 10% sucrose-BYE L-form plates. The colonies were composed of only a few filaments and many vesicles which were negative with Dienes' stain. Silver substitution stains of UCD 81-332-9 cells that had been grown in L-form broth for 5 days revealed heavy calcification of all cells including protoplasts. Gram stains of L-form grown cells revealed the presence of long-beaded, infrequently branched gram-positive filaments similar to those observed in clinical specimens. The formation of cell wall-deficient variants with coincident mineralization is believed to be related to the phenomenon of sulfur granule formation in vivo.

Angioedema in the emergency department: the impact of angiotensin-converting enzyme inhibitors.

Angiotensin-converting enzyme (ACE) inhibitors have been reported to cause angioedema. The purpose of this study was to establish what proportion of patients who present to the emergency department (ED) with angioedema were concomitantly taking any of the ACE inhibitors and to show how this group differed in presentation and response to treatment from the larger population of patients with non-ACE inhibitor-related angioedema. An 8-year retrospective chart review of all patients with the diagnosis of angioedema observed from January 1, 1984 to December 31, 1991 was undertaken in the ED of an urban teaching hospital. Forty-nine patients ranging from 12 to 88 years of age with symptoms and physical examination that was consistent with the diagnosis of angioedema were entered onto the study. Twelve cases of ACE inhibitor-related angioedema were identified, all occurring in the last 4 years of the review, and when compared with the non-ACE inhibitor-related group were older (mean age, 63.3 vs 43.0 years), had less of an allergic history (0% vs 49%; P = .013), but demonstrated the same severity of symptoms and response to medical therapy. No case required an artificial or surgical airway. ACE inhibitor related angioedema is becoming a common type of angioedema observed in this ED. These patients are older and free of other allergic disease and respond well to traditional therapy.