Monocyte chemotactic protein expression during schistosome egg granuloma formation. Sequence of production, localization, contribution, and regulation.

The present study explored the role of murine monocyte chemotactic protein (MCP) in the T cell-mediated hypersensitive granulomatous response to Schistosoma mansoni eggs. The study examined the time course of local production, contribution to cellular infiltration, and the role of T cells in endogenous regulation. Synchronized pulmonary granulomas were induced under conditions of primary and secondary states of immunity. Primer-directed polymerase chain reaction analysis showed increased MCP mRNA expression in granulomatous lungs, mainly in the secondary response. Levels of MCP were measured by enzyme-linked immunosorbent assay in cultures of intact granulomas. Spontaneous MCP production was modest in primary granuloma cultures, reaching a maximum of 5.7 +/- 0.9 ng/ml by 16 days. In contrast, the secondary response showed augmented and accelerated production, achieving 13 +/- 2.0 ng/ml by 2 days. Immunohistochemical staining revealed the strongest MCP expression within microvascular adventitial cells or pericytes as well as in scattered mononuclear cells associated with granulomas. Staining was not detected in normal lungs. Passive immunization with anti-MCP-1 antibodies caused a 40% reduction in the secondary granuloma area but did not significantly affect the primary response. With adoptive cell transfer and T cell subset depletion, it was shown that Thy-1+ and CD5+ cells augmented, whereas CD8+ cells appeared to impair, MCP production. This provides direct evidence that MCP is involved in secondary Th2-mediated response to schistosome eggs and is subject to regulation by T cells.     

Incidence of hypertension in the Framingham Study.

Incidence and trends in incidence of definite hypertension were analyzed based on 30 years follow-up of 5,209 subjects in the Framingham Heart Study cohort. Based on pooling of 15 two-year periods, hypertension incidence per biennium increased with age in men from 3.3 per cent at ages 30-39 to 6.2 per cent at ages 70-79, and in women from 1.5 per cent at ages 30-39 to 8.6 per cent at ages 70-79. No consistent trend in incidence rates was evident for either sex from the 1950s through the 1970s. The proportion of hypertensive subjects receiving antihypertensive medication has increased since 1954-58 and exceeded 80 per cent for both men and women ages 60-89 years in 1979-81. Incidence data presented in this report may serve as a baseline for assessing the impact of future public health efforts in the primary prevention of hypertension.     

Unraveling the mysteries of serum theophylline levels: a patient care report in the light of pharmacokinetics

One of our patients had trouble maintaining therapeutic and safe levels of theophylline, even though we were careful in planning and monitoring her drug regimen. This case report shows how we were able to use principles of pharmacokinetics to distinguish among plausible explanations for her experience. We discovered that she was not taking the drug consistently as prescribed and that supervised administration resolved apparent contradictions between doses and serum levels. We believe that physicians can use the same information and methods that we used to get better and safer results from theophylline therapy.     

Theoretical and practical considerations in the doubly-labelled water (2H2(18)O) method for the measurement of carbon dioxide production rate in man

In the doubly-labelled water (2H2(18)O) method for the measurement of carbon dioxide production rate in man, single exponential disappearance curves for 2H2O and H2(18)O in body water are used; the precision with which the slopes and intercepts of the curves are estimated determines the precision of the estimate of carbon dioxide production rate. In studies with infants, and in computer simulations, the effect of different experimental regimes on the overall precision of the carbon dioxide production estimate was investigated. When the number of data points used was progressively reduced by shortening the total observation period from 7 d (about 3 biological half-lives for the isotopes) to 1 d there was a deleterious effect on precision and in the infants there was an upward bias in the values for carbon dioxide production. When the number of data points was reduced by removing points from the middle of the exponential curves with the maintenance of the 7-d experimental period, precision was also reduced but by less than in the former procedure and there were no consistent trends in the average values for carbon dioxide production.     

Herpes zoster: a consideration in the differential diagnosis of radiculopathy

Herpes zoster probably occurs more often than generally thought. Since it produces a radicular distribution of pain, it should be included in the differential diagnosis of radiculopathy. A case is presented in which evaluating the radicular low back pain before the characteristic rash appears was misleading. Careful history-taking concerning the exact nature of the pain and sensory changes is needed to differentiate between zoster and radiculopathy, if no rash is evident.     

Chorioretinal folds and a macular hole secondary to craniofacial surgery

Chorioretinal folds have been reported as a result of many intraocular and extraocular inflammatory processes or tumors. Visual loss is usually secondary to a combination of the underlying process and chorioretinal folds involving the macula. We report a patient who developed decreased vision, metamorphopsia, chorioretinal folds, and a lamellar macular hole secondary to global compression by a bone fragment. The chorioretinal folds regressed and his vision stabilized following surgical decompression. Chorioretinal folds and lamellar macular hold formation are previously unrecognized complications of reconstructive craniofacial surgery.     

Large granular lymphocyte expansions in patients with Felty's syndrome: analysis using anti-T cell receptor V beta-specific monoclonal antibodies.

Felty's syndrome (FS), the association of rheumatoid arthritis (RA) and idiopathic neutropenia, remains an unexplained phenomenon. HLA-DR4 is found in over 90% of cases. Patients with FS may have a T cell lymphocytosis of CD3+CD8+CD57+ large granular lymphocytes (LGL syndrome). In this study of 47 patients with FS, 19% had clear evidence for LGL expansions, while in total 42% had variable evidence for the LGL syndrome using currently available techniques. Of these T cell expansions, 76% were clonal, as demonstrated by Southern blotting and analysis with T cell receptor (TCR) beta chain constant region probes. This technique may fail to detect clonal populations in some patients. Cytofluorographic analysis using antibodies specific for TCR V beta chains identified patients with clonal LGL expansions with results comparable to those obtained with Southern blotting. No evidence for shared V beta usage among expansions from different patients was seen. The role of LGL in RA and FS is currently unclear, but this technique offers a practical and accessible means of identifying patients with LGL expansions, as a starting point for further investigation.