Clinical and radiological diagnosis of Crohn's disease in children

Diagnosis of Crohn's disease in children may be delayed because of obscure presentation and inappropriate investigation. The clinical and radiological features in 35 children with Crohn's disease were reviewed retrospectively. The distal ileum and proximal colon were the most common sites of disease. Intestinal symptoms and signs were often overshadowed by nonspecific complaints. Proximal small bowel disease was characterised by oedema, clubbing, anaemia, and stunting of growth. The delay in diagnosis was less than in other series, although most prolonged in the group with proximal disease. We have identified a group of clinical features that strongly suggests Crohn's disease. In these patients, we believe a small bowel enema is justified. Small bowel enema, although invasive, is more effective than barium meal and follow-through for demonstrating Crohn's disease. Severity of radiological changes did not correlate with clinical assessment. Neither bowel stricture nor fistula was found. Radiology of the colon was insensitive and colonoscopy is better for assessing colonic disease.     

Interactions of Treponema pallidum with endothelial cell monolayers

Syphilis is a chronic disease characterized by hematogenous dissemination of Treponema pallidum into tissues such as the cardiovascular and central nervous systems. In order to test whether these aspects of the pathogenesis of syphilis reflect an ability of T. pallidum to invade vascular entothelial surfaces, we explored the association of T. pallidum with human and rabbit endothelial cells in vitro. Using radiolabeled motile organisms, we found that treponemal attachment was two times greater to rabbit aortic endothelial cells and human umbilical endothelial cells than to HeLa cells. Mild trypsinization of attached treponemes resulted in release from cells of all organisms detectable by darkfield microscopy without visible damage to the monolayer. Nevertheless, 25% of the counts representing T. pallidum remained associated with the cell monolayers. Further trypsin treatment to release the monolayer and differential centrifugation showed that 80% of the remaining cell-associated counts were not within the cells. These results suggest that some treponemes had associated with the monolayer in a trypsin resistant niche. Additionally, motile T. pallidum passed through tight functioned endothelial cell monolayers on membrane filters under conditions were heat-killed T. pallidum and the host indigenous nonpathogen. T. phagedenis biotype Reiter failed to do so. Electron micrographs of transverse sections through the monolayers showed many T. pallidum in junctions between endothelial cells. These studies suggest that T. pallidum may leave the circulation by passing between endothelial cells.     

Metabolism of doxylamine succinate in Fischer 344 rats. Part II: Nonconjugated urinary and fecal metabolites

Elimination and metabolic profiles of doxylamine and its nonconjugated metabolites were determined after the oral administration of [14C]-doxylamine succinate (13.3 mg/kg and 133 mg/kg doses) to male and female Fischer 344 rats. Total urine and fecal recovery of the administered dose was greater than 90% regardless of sex or dose. The cumulative urinary and fecal elimination of these nonconjugated doxylamine metabolites at the 13.3 mg dose was 44.4 +/- 4.4% and 36.0 +/- 5.8% of the total recovered dose for male and female rats, respectively. The cumulative urinary and fecal elimination of the doxylamine nonconjugated metabolites at the 133 mg/kg dose was 38.7 +/- 2.7% and 41.4 +/- 1.0% of the total recovered dose for male and female rats, respectively. In order to determine the contribution of mammalian and bacterial enzymes in the overall metabolism and excretion patterns for doxylamine, two in vitro techniques were investigated. Incubation of [14C]-doxylamine succinate with human and rat intestinal microflora indicated that anaerobic bacteria were not capable of effecting the degradation of [14C]-doxylamine succinate. However, the incubation of [14C]-doxylamine succinate with isolated rat hepatocytes generated several metabolites similar to those observed in vivo. The nonconjugated doxylamine metabolites isolated and identified include: doxylamine N-oxide, desmethyldoxylamine, didesmethyldoxylamine and ring-hydroxylated products of doxylamine and desmethyldoxylamine. The studies demonstrate the role of hepatic metabolism in the elimination of doxylamine succinate in the rat.     

Enhancement of ketoconazole penetration across the blood-brain barrier of mice by dimethyl sulfoxide.

Mice were treated with ketoconazole with and without dimethyl sulfoxide. Concentrations of ketoconazole at 3 and 5 h after treatment were significantly higher in serum (P less than 0.05) and brain tissue homogenate (P less than 0.01) of mice treated with dimethyl sulfoxide than in those of mice not treated with dimethyl sulfoxide.     

Tuberculosis risk among migrant farm workers on the Delmarva peninsula.

A survey was conducted to ascertain the risk of tuberculosis (TB) among migrant farm workers on the Delmarva peninsula. Relevant histories were obtained from 842 migrants; a total of 709 skin tests were completed, and 239 sputum specimens were examined for acid-fast bacilli (AFB) and culture. No cases of infectious tuberculosis were ascertained by history or AFB examination. One sputum culture was positive for M. tuberculosis and 13 were positive for various species of nontuberculous mycobacteria. Thirty-seven per cent of migrants tested had significant skin test reactions of 10 mm or more. Reaction rates for men were 41 per cent and for women 25 per cent. Age specific rates ranged from 14 per cent in children aged 5-14 to 54 per cent for ages 45-54. Rates for the principal national/ethnic groups were Haitians 55 per cent, Mexicans 36 per cent, US Blacks 29 per cent and US-born Latinos 20 per cent. Based on these results and other information currently available, it is recommended that current Centers for Disease Control (CDC) recommendations for TB prophylaxis continue to be applied for migrant workers, but that mass screening by skin testing in camp populations not be emphasized. Other recommendations focus on: case finding of active disease, improving continuity and follow-up, increasing coordination among involved agencies, and actively supporting improved economic and living conditions for migrant farm workers.     

Prednisone-induced worsening of neuromuscular function in myasthenia gravis

In patients with myasthenia gravis who received single doses of prednisone orally (40 to 100 mg), we found acute inhibition of neuromuscular function as manifest by increased decremental responses to repetitive nerve stimulation, reduced twitch tension, and lowered maximum voluntary contraction strength. The time course of these changes correlated with plasma methylprednisolone levels, implying direct drug effects on neuromuscular function.     

Rapid digital filtering

Image filtering with the larger, and potentially most valuable, digital filters is very time-consuming, thus precluding use of these filters in routine clinical applications. A recently developed algorithm for spatial-domain filtering is described, and its speed is compared with those of conventional methods with and without an array processor. Using the new Chebyshev method, a 64 by 64 pixel image can be filtered on a standard 16-bit minicomputer with filters of size 3 by 3 to 23 by 23 in 1.4-9.2 sec. The conventional spatial-domain algorithm requires 3.8-71 sec. With an array processor, filtering is accomplished in 0.19-0.54 sec. Filtering in the frequency domain requires 34 sec without an array processor and 0.12 sec with one. Thus with this new Chebyshev algorithm, clinically practical digital filtering can be performed with large filters even without an array processor.     

Evidence for the ventral origin of oligodendrocyte precursors in the rat spinal cord

The neuroepithelial cells of the mammalian neural tube are thought to give rise to all classes of differentiated neurons and macroglial cells in the adult CNS. In most cases, the regulation and timing of commitment of neuroepithelial cells to specific differentiative pathways are unknown. It has been proposed that in developing spinal cord, the macroglial cells--astrocytes and oligodendrocytes--arise either by the direct transformation of radial glial cells in the developing cord or, alternatively, by the differentiation of distinct precursor cells which migrate to presumptive white matter from the region of the central canal during development. In this study, the timing of oligodendrocyte differentiation in different levels of the spinal cord and the capacity of specific regions of the spinal cord to give rise to oligodendrocytes at various ages was tested in vitro. At embryonic day 14, all complete segments, as well as all ventral regions along the rostral-caudal axis of the spinal cord, have the capacity for oligodendrogenesis. By contrast, dorsal regions of the thoracic and lumbar spinal cord do not develop the capacity for oligodendrogenesis until later in development. The capacity of dorsal rat spinal cord to give rise to oligodendrocytes appears to be associated with the ventral-to-dorsal migration of oligodendrocyte precursors. These observations suggest that commitment to an oligodendrocyte differentiative pathway appears to occur in a distinct population of ventrally located glial precursors in the embryonic rat spinal cord.     

Anti-idiotypes in B-cell tumor therapy

Thirteen patients with B-cell lymphomas were treated with mouse monoclonal anti-idiotype antibodies. All but 1 of the patients in this study had received extensive prior treatment with conventional therapy for lymphoma. The treatment protocol initially included an escalating dose schedule which was intended to help us evaluate toxicity and pharmacokinetics and, eventually, to achieve appreciable levels of free mouse antibody in the circulation. The last 4 patients received substantial initial doses. Tumor sampling was performed before and during therapy for evaluation of tissue penetration by antibody. Patients received antibodies of gamma 1, 2a, or 2b isotype. None of the patients had serum paraproteins by routine clinical testing, but 6 had an idiotype protein detectable by a sensitive immunoassay at levels greater than 1 microgram/ml, two of which were greater than 200 micrograms/ml. These levels were temporarily reduced by plasma-pheresis. However, the presence of serum idiotype increased the requirement for mouse antibody to achieve tumor penetration. Another obstacle to treatment was immune response to mouse Ig that occurred in 5 of the 13 patients. Once an immune response had begun, further infusions of antibody failed to reach the tumor or induce tumor regression and were associated with toxicity. Our initial patient remains in an unmaintained complete remission 50 months after receiving antibody. Six of 12 additional patients have had objective remissions which also were clinically significant. However, these remissions were not complete. This therapy shows promise as an alternative modality for the treatment of B-cell lymphoma. We will need further studies to determine the mechanisms of the antitumor effect and to improve the clinical results.