Epstein-Barr virus (EBV)-associated lymphoproliferations in severe combined immunodeficient mice transplanted with Hodgkin's disease lymph nodes: implications of EBV-positive bystander B lymphocytes rather than EBV-infected Reed-Sternberg cells

To establish an in vivo model for the study of Hodgkin's disease and Reed-Sternberg (RS) cells, 25 lymph node tissue samples involved by Hodgkin's disease were grafted into severe combined immunodeficiency (SCID) mice. Ten Epstein-Barr virus (EBV)-associated tumors were obtained in SCID mice. EBV-positive tumors growing in SCID mice were correlated with the presence of EBV-positive nonneoplastic B cells in patient tumors (90% v 26.6%; P<.01) and was independent of the EBV status of RS cells. Our results suggested that EBV-positive tumors growing in SCID mice originated from normal EBV-positive small lymphocytes (bystander B lymphocytes). We also compared the characteristics of these tumors with those obtained after transplantation of 15 non-Hodgkin's lymphoma and four reactive lymph nodes. The latent period to observe a growing tumor in SCID mice was similar between the two groups (12.86 +/- 5.59 weeks for Hodgkin's disease v 13.6 +/- 5.36 weeks for non-Hodgkin's lymphoma and reactive lymph nodes). The relatively high number of EBV-positive small lymphocytes detected in Hodgkin's disease and T-cell lymphoma compared with B-cell lymphoma may account for the greater percentage of EBV- positive tumors obtained in SCID mice. Our results show that SCID mice do not provide the growth conditions that are required for in vivo growth of RS cells. We noted in some SCID tumors, the presence of binucleated and/or multinucleated giant cells resembling RS cells. However, the presence of such cells was not restricted to mice grafted with lymph nodes involved by Hodgkin's disease. We postulate that in previous reports, cells resembling RS cells were just binucleated EBV- positive lymphoma blastoid cells rather than actual RS cells.     

Brain monoglyceride lipase participating in endocannabinoid inactivation

The endogenous cannabinoids (endocannabinoids) are lipid molecules that may mediate retrograde signaling at central synapses and other forms of short-range neuronal communication. The monoglyceride 2-arachidonoylglycerol (2-AG) meets several criteria of an endocannabinoid substance: (i) it activates cannabinoid receptors; (ii) it is produced by neurons in an activity-dependent manner; and (iii) it is rapidly eliminated. 2-AG inactivation is only partially understood, but it may occur by transport into cells and enzymatic hydrolysis. Here we tested the hypothesis that monoglyceride lipase (MGL), a serine hydrolase that converts monoglycerides to fatty acid and glycerol, participates in 2-AG inactivation. We cloned MGL by homology from a rat brain cDNA library. Its cDNA sequence encoded for a 303-aa protein with a calculated molecular weight of 33,367 daltons. Northern blot and in situ hybridization analyses revealed that MGL mRNA is heterogeneously expressed in the rat brain, with highest levels in regions where CB(1) cannabinoid receptors are also present (hippocampus, cortex, anterior thalamus, and cerebellum). Immunohistochemical studies in the hippocampus showed that MGL distribution has striking laminar specificity, suggesting a presynaptic localization of the enzyme. Adenovirus-mediated transfer of MGL cDNA into rat cortical neurons increased MGL expression and attenuated N-methyl-D-aspartate/carbachol-induced 2-AG accumulation in these cells. No such effect was observed on the accumulation of anandamide, another endocannabinoid lipid. The results suggest that hydrolysis by means of MGL is a primary mechanism for 2-AG inactivation in intact neurons.     

Sequential histologic evaluations in collagenous colitis

To evaluate the histologic manifestations of collagenous colitis and correlate histologic changes with disease behavior, 14 patients who had undergone sequential evaluations during 33±6 months of follow-up were studied. Two hundred twelve tissue specimens from all anatomic regions of the colon (mean, 15±3 samples per patient) were interpretated independently under code by two pathologists. Eight patients (57%) had histologic resolution after 14±4 months of empiric therapy and in only one of these (12%) did symptoms persist. Four patients (29%) had sequential histologic examinations from the same anatomic region that varied from classical collagenous colitis to ilflamed mucosa without a thickened collagen band to normal mucosa. Eight patients (57%) had varying histologic findings from different anatomic regions during the same examination that ranged from classical collagenous colitis to increased inflammation with resolution of the collagen band to normal mucosa. Normal mucosa was found mainly in specimens from the rectosigmoid, and proctosigmoidoscopic examinations alone would have missed the diagnosis of collagenous colitis in 40% of cases. Pathologic interpretations were concordant in 171 of 212 instances (81%). We conclude that histologic resolution of collagenous colitis can occur and it is associated with loss of symptoms. The histologic features of collagenous colitis are distinctive, but they may be patchy and inconsistently sampled. Rectosigmoid biopsies underestimate the diagnosis.Data analysis was performed in part using the CLINFO Data Analysis System.Presented in part at the annual meeting of the American College of Gastroenterology, October 16, 1991, Boston, Massachusetts.     

Computed tomographic scanning versus radioisotope imaging in adrenocortical diagnosis

Referral patterns from internists to departments of nuclear medicine or radiology are important determinants of whether adrenal glands are imaged by computed tomography (CT) or by radioisotope scintigraphy. To assist clinicians in making an informed choice, computed tomographic scans were compared with isotope scintigrams using 131I-19-iodocholesterol (19-IC) and 131I-6 beta-iodomethyl-19-norcholesterol (NP-59). In general, imaging techniques serve to localize diseases that are diagnosed on the basis of biochemical tests of adrenal function. Computed tomographic scanning and NP-59 scanning are of comparable diagnostic accuracy. Both are superior to 19-IC scanning in the diagnosis of Cushing's syndrome and primary aldosteronism. Computed tomographic scanning is faster and less expensive, and involves lower radiation doses to the patient than scintigraphy. Adrenocortical isotope scanning as a routine procedure has been superseded by computed tomographic scanning at the Mayo Clinic.     

The impact of a celebrity promotional campaign on the use of colon cancer screening: the Katie Couric effect

BACKGROUND: Public participation in many preventive health programs is suboptimal. While various interventions to increase participation have been studied, the impact of a celebrity spokesperson on cancer screening has not been rigorously examined. The objective of this study was to assess the impact of Katie Couric's March 2000 Today Show colorectal cancer awareness campaign on colonoscopy rates. METHODS: A population-based observational study was conducted using 2 different data sources: (1) The Clinical Outcomes Research Initiative (CORI) database-a voluntary consortium of 400 endoscopists who performed 95 000 colonoscopies from July 1998 to December 2000; and (2) 44 000 adult members of a managed care organization. Using change point analyses and linear regression models, we compared colonoscopy utilization rates before and after Ms Couric's March 2000 television series. RESULTS: The number of colonoscopies performed per CORI physician per month after Ms Couric's campaign increased significantly (15.0 per month before campaign; 18.1 after campaign; P<.001). After adjusting for temporal trends, a significantly higher postcampaign colonoscopy rate was sustained for 9 months. Analysis also demonstrated a trend toward an increase in the percentage of colonoscopies performed on women (43.4% before campaign; 47.4% after campaign; P =.054). Colonoscopy rates also increased significantly in the managed care organization after Ms Couric's campaign (1.3 per 1000 members per month before; 1.8 after; P<.001). CONCLUSIONS: Katie Couric's televised colon cancer awareness campaign was temporally associated with an increase in colonoscopy use in 2 different data sets. These findings suggest that a celebrity spokesperson can have a substantial impact on public participation in preventive care programs.     

Variable expression of 5 alpha-reductase deficiency: presentation with male phenotype in a child of Greek origin

A male infant with perineal hypospadias and a small phallus bound in chordee is described. Biochemical investigation at age 9 months after hCG stimulation revealed a testosterone to dihydrotestosterone (DHT) ratio of 40, a markedly elevated value suggestive of deficient steroid 5 alpha-reductase activity. The diagnosis of 5 alpha-reductase deficiency was confirmed by elevated urinary 5 beta/5 alpha-steroid metabolite ratios and demonstration of defective 5 alpha-reductase activity in cultured fibroblasts from the patient's scrotum and foreskin. Application of DHT cream to the patient's abdomen raised circulating levels of DHT to the adult male range. Two courses of DHT given nightly for 3 and 4 months resulted in phallic enlargement. Surgical release of the chordee and hypospadias repair have resulted in normal male appearance of the genitalia. This case illustrates the heterogeneity of the 5 alpha-reductase deficiency phenotype.     

Contributions to enhanced activity in rectus femoris in response to Lokomat-applied resistance

The application of resistance during the swing phase of locomotion is a viable approach to enhance activity in the rectus femoris (RF) in patients with neurological damage. Increased muscle activity is also accompanied by changes in joint angle and stride frequency, consequently influencing joint angular velocity, making it difficult to attribute neuromuscular changes in RF to resistance. Thus, the purpose of this study was to evaluate the effects of resistance on RF activity while constraining joint trajectories. Participants walked in three resistance conditions; 0 % (no resistance), 5 and 10 % of their maximum voluntary contraction (MVC). Visual and auditory biofeedback was provided to help participants maintain the same knee joint angle and stride frequency as during baseline walking. Lower limb joint trajectories and RF activity were recorded. Increasing the resistance, while keeping joint trajectories constant with biofeedback, independently enhanced swing phase RF activity. Therefore, the observed effects in RF are related to resistance, independent of any changes in joint angle. Considering resistance also affects stride frequency, a second experiment was conducted to evaluate the independent effects of resistance and stride frequency on RF activity. Participants walked in four combinations of resistance at 0 and 10 %MVC and natural and slow stride frequency conditions. We observed significant increases in RF activity with increased resistance and decreased stride frequency, confirming the independent contribution of resistance on RF activity as well as the independent effect of stride frequency. Resistance and stride frequency may be key parameters in gait rehabilitation strategies where either of these may be manipulated to enhance swing phase flexor muscle activity in order to maximize rehabilitation outcomes.