Recombinant vaccinia viruses expressing GP46/M-2 protect against Leishmania infection.

Leishmania is a genus of parasitic protozoa capable of causing a spectrum of human diseases. The GP46/M-2 membrane glycoprotein has been demonstrated in a murine model system to elicit a protective immune response against infection with Leishmania amazonensis; in highly susceptible BALB/c mice, immunization leads to significant protection against infection. In the present study, for induction of long-term immunological effects, two recombinant vaccinia viruses, derived from the wild type and attenuated variant 48-7 and expressing the GP46/M-2 protein, were constructed; to ensure safety, we used the attenuated vaccinia virus mutant (48-7) as a live vector. Susceptible BALB/c mice immunized with either GP46/M-2-recombinant vaccinia virus were significantly protected against infection with L. amazonensis; 45 to 76% of the animals were completely protected (sterile) against a challenge inoculum of 10(3) infective organisms. The protectively immunized animals demonstrated T- and B-cell-dependent immunological responses; both lymphokine responses as well as antibody responses and long-term memory are indicative of T-cell activation. This first report of the use of a recombinant vaccinia virus to induce protection against a Leishmania infection indicates that recombinant vaccinia viruses should be of value in the design of a safe and effective vaccine against this parasitic disease.     

Identification, isolation, and characterization of daintain (allograft inflammatory factor 1), a macrophage polypeptide with effects on insulin secretion and abundantly present in the pancreas of prediabetic BB rats

A bioactive macrophage factor, the polypeptide daintain/allograft inflammatory factor 1 (AIF1), has been isolated from porcine intestine. It was discovered when searching for intestinal peptides with effects on insulin release, and its purification was monitored by the influence of the peptide fractions on pancreatic glucose-induced insulin secretion. Daintain/AIF1 is a 146-aa residue polypeptide with a mass of 16,603 Da and an acetylated N terminus. An internal 44-residue segment with the sequence pattern –KR–KK–GKR– has a motif typical of peptide hormone precursors, i.e., dibasic sites for potential activation cleavages and at the sequentially last such site, the structure GKR. The latter is a signal for C-terminal amide formation in the processing of peptide hormones. Daintain/AIF1 is immunohistochemically localized to microglial cells in the central nervous system and to dendritic cells and macrophages in several organs. A particularly dense accumulation of daintain/AIF1-immunoreactive macrophages was observed in the insulitis affecting the pancreatic islets of prediabetic BB rats. When injected intravenously in mice, daintain/AIF1 at 75 pmol/kg inhibited glucose (1 g/kg)-stimulated insulin secretion, with a concomitant impairment of the glucose elimination, whereas at higher doses (7.5 and 75 nmol/kg), daintain/AIF1 potentiated glucose-stimulated insulin secretion and enhanced the glucose elimination. Its dual influence on insulin secretion in vivo at different peptide concentrations, and the abundance of macrophages expressing daintain/AIF1 in the pancreatic islets of prediabetic rats, suggest that daintain/AIF1 may have a role in connection with the pathogenesis of insulin-dependent diabetesmellitus.     

Symptomatic peripheral arterial disease: the value of a validated questionnaire and a clinical decision rule

BACKGROUND: If a validated questionnaire, when applied to patients reporting with symptoms of intermittent claudication, could adequately discriminate between those with and without peripheral arterial disease, GPs could avoid the diagnostic measurement of the ankle brachial index. AIM: To investigate the Edinburgh Claudication Questionnaire (ECQ) in general practice and to develop a clinical decision rule based on risk factors to enable GPs to easily assess the likelihood of peripheral arterial disease. DESIGN OF STUDY: An observational study. SETTING: General practice in The Netherlands. METHOD: This observational study included patients of > or =55 years visiting their GP for symptoms suggestive of intermittent claudication or with one risk factor. The ECQ and the ankle brachial index were performed. The prevalence of peripheral arterial disease, defined as an ankle brachial index <0.9, was related to risk factors using logistic regression analyses, on which a clinical decision rule was developed and related to the presence of peripheral arterial disease. RESULTS: Of the 4790 included patients visiting their GP with symptoms suggestive of intermittent claudication, 4527 were eligible for analyses. The prevalence of peripheral arterial disease in this group was 48.3%. The sensitivity of the ECQ was only 56.2%. The prevalence of peripheral arterial disease in a clinical decision rule that included age, male sex, smoking, hypertension, hypercholesterolemia, and a positive ECQ, increased from 14% in the lowest to 76% in the highest category. CONCLUSION: This study indicates that the ECQ alone has an inadequate diagnostic value in detecting patients with peripheral arterial disease. The ankle brachial index should be performed to diagnose peripheral arterial disease in patients with complaints suggestive of intermittent claudication, although our clinical decision rule could help to differentiate between extremely high and lower prevalence of peripheral arterial disease.     

Chronic musculoskeletal pain predicted hospitalisation due to serious medical conditions in a 10 year follow up study

Background  

The aim was to examine if self reported chronic regional pain (CRP) and chronic widespread pain (CWP) predicted inpatient care due to serious medical conditions such as cerebrovascular diseases, ischemic heart diseases, neoplasms and infectious diseases in a general population cohort over a ten year follow-up period.     

Further studies on fecal parasites in antiquity.

This is a continuation study of the survival of antigenic material over the centuries using mummified human remains from the Andean area of South America. The fluorescent antibody kit from Meridian Diagnostics (Cincinnati, OH) was used to identify some Cryptosporidium species and Giardia species found in feces from the intestines of mummies 500 to 3,000 years old. The specimens that were positive by direct visualization using fluorescent antibody were then tested with an enzyme-linked immunosorbent assay reaction using a Meridian kit just released on the market. Since all of the feces used were formed, it would seem that the organisms found were from carriers rather than active cases of disease. Similar fecal specimens were shown to harbor antigens from Helicobacter pylori almost 3,000 years old.     

Gains and amplifications of c-myc, EGFR, and 20.q13 loci in the no dysplasia-dysplasia-adenocarcinoma sequence of Barrett's esophagus

The progression of Barrett's esophagus to esophageal adenocarcinoma is often characterized by the accumulation of genetic abnormalities. The goal was to evaluate the copy number alterations of several oncogene loci, including 7p12 [epidermal growth factor receptor (EGFR)], 8q24 (c-myc), and 20q13 in the sequence of no dysplasia-dysplasia-adenocarcinoma of Barrett's esophagus. Fluorescence in situ hybridization with DNA probes for the centromeric region of chromosome 7 and the locus-specific regions of 7p12 (EGFR), 8q24 (c-myc), and 20q13 was applied on 99 brush cytology specimens of patients with Barrett's esophagus with different stages of dysplasia or esophageal adenocarcinoma. Gains (3-4 copies) of chromosome 17, 8q24 (c-myc), and 20q.13 loci were found in the low frequencies in nondysplastic Barrett's esophagus. Their frequencies increased with the stage of dysplasia and reached a high incidence in esophageal adenocarcinoma. Amplification (>4 copies) of at least 1 of the loci was observed in 14% of high-grade dysplasia and increased to 50% in esophageal adenocarcinoma (P = 0.015). The most frequently amplified locus was c-myc (18%), followed by 20q13 (13%) and EGFR (11%) in the high-grade dysplasia/esophageal adenocarcinoma cases. High amplification levels (>10 copies) of the loci were more frequent in esophageal adenocarcinoma (72%) compared with high-grade dysplasia (20%; P = 0.049). Amplifications of the c-myc, EGFR, and 20q12 loci may serve as diagnostic markers to identify patients with Barrett's esophagus with high-grade dysplasia or esophageal adenocarcinoma. Gains of the loci might be of value as prognostic markers because they are already present in nondysplasia cases and may precede the later event of the amplification as observed in high-grade dysplasia and esophageal adenocarcinoma.     

Influence of repeated infestations with pathogen-free Ixodes scapularis (Acari: Ixodidae) on in vitro lymphocyte proliferation responses of C3H/HeN mice

In the United States, Ixodes scapularis Say has been implicated as the vector of at least three human pathogens. Tick induced modulation of host immunity is increasingly recognized as an important factor in successful transmission or establishment of tick-borne pathogens. This study was conducted to determine the effects of repeated infestations with pathogen-free I. scapularis nymphs on in vitro proliferative responses of splenic lymphocytes from C3H/HeN mice. Lymphocytes from repeatedly infested and uninfested mice were exposed to concanavalin A (Con A), Escherichia coli Castellini & Chalmers lipopolysaccharide (LPS), or I. scapularis salivary gland soluble proteins (SGSP), to determine if lymphocyte responses differed between tick-exposed and nonexposed mice. Female C3H/HeN mice were infested one to four times with pathogen-free I. scapularis nymphs, with a 14-d tick-free period between each exposure. After each infestation, tick biology parameters were measured and lymphocyte proliferative responses assessed. Acquired resistance to I. scapularis was not evident in mice subjected to tick feeding. Significant differences in the responses of lymphocytes exposed to I. scapularis SGSP were observed between infested and noninfested mice. In contrast, few differences between infested and noninfested mice were evident for lymphocytes exposed to Con A or LPS. Our results suggest that repeated exposure to I. scapularis nymphs does not affect Con A or LPS-induced proliferation of splenic lymphocytes, but significantly effects lymphocyte responses to tick salivary gland antigens.     

Prevention of pedestrian injuries to children: effectiveness of a school training program

Pedestrian injuries are a complex problem for which no single intervention will be completely effective. One component of a community-wide program, training of schoolchildren in street-crossing skills, is evaluated. The program targeted public school students in grades K through 4 with an eight-session training program by a single teacher, cross-age teaching, videotape feedback, and in 1990 parent-child activity workbooks. Children's street crossing was observed pretraining and posttraining and graded on four behaviors: WALKING on sidewalk/shoulder vs in the street; STOPPING at the curb; LOOKING L-R-L before crossing; KEEP LOOKING while crossing. Analysis was conducted on matched pairs in which observations pretraining were compared with those posttraining on same child. Observations were completed on 137 children in 1989 and 92 in 1990. Nearly all children walked on the side of the road; however, fewer than 50% of children STOPPED, 25% LOOKED, and fewer than 20% KEPT LOOKING before training. Training did not improve the performance on the first two behaviors in either year, significantly increased LOOKING in 1990, and increased KEEP LOOKING by twofold in 1989 and threefold in 1990. It is concluded that pedestrian skills of children can be improved but that such a program must be part of a broader effort if pedestrian injuries are to decrease.     

Toxic epidermal necrolysis. A comprehensive approach. Multidisciplinary management in a burn center

Toxic Epidermal Necrolysis (TEN) is a life-threatening disorder with reported mortality rates of 25-60 percent in pediatric patients. The authors report on their experience in managing six children using a standardized treatment protocol in the intensive care unit of a regional burn center. Areas of sloughed skin were covered with porcine xenograft (pig skin) until reepithelialization was complete. There was one death in the series, and one child had ophthalmologic complications. Treatment in a multidisciplinary burn center is recommended for children with TEN.