Pretransplantation surveillance for possible hepatocellular carcinoma in patients with cirrhosis: epidemiology and CT-based tumor detection rate in 430 cases with surgical pathologic correlation.

PURPOSE: To determine the prevalence of clinically unsuspected hepatocellular carcinoma (HCC) with advanced cirrhosis and assess the sensitivity of helical computed tomographic (CT) surveillance for tumor detection in these patients. MATERIALS AND METHODS: Prospective direct correlation of CT findings with explanted liver specimen findings was performed in 430 transplant recipients with cirrhosis. The prevalence of clinically unsuspected HCC according to liver disease cause was evaluated. Serum alpha-fetoprotein (AFP) values in patients with and those without tumor were recorded. Prospective and retrospective CT tumor detection was evaluated with respect to CT technique and time from CT to transplantation. RESULTS: HCC was found in 59 (14%) of 430 transplant recipients without suspicion of tumor before referral for transplantation. HCC was most prevalent with hepatitis B (27%) and hepatitis C (22%). Serum AFP values were not sensitive for detection of most small tumors. With triphasic helical CT, the prospective and retrospective rates of identifying patients with tumor were 59% and 68%, respectively; the prospective and retrospective tumor nodule detection rates were 37% and 44%, respectively. Tumor detection rates were highest with CT performed within 67 days before transplantation. CONCLUSION: Clinically unsuspected HCC is most prevalent with cirrhosis secondary to hepatitis B or C, and, when evaluated at CT, is best detected with triphasic contrast material-enhanced helical imaging performed within 67 days before transplantation.

The importance of diagnostic accuracy in colonic inflammatory bowel disease.

OBJECTIVE: Crohn's disease (CD) and ulcerative colitis (UC) may both affect the colon. However, in approximately 10-20% of these cases, it is impossible to distinguish between these two entities either clinically or histologically, and a diagnosis of indeterminate colitis (IC) is made. Correct diagnosis is important because surgical treatment and long-term prognosis differ for UC and CD. The purpose of this study was to determine the extent of interobserver agreement among board-certified pathologists and a specialist gastrointestinal (GI) pathologist regarding the histological diagnosis of colonic inflammatory bowel disease (IBD). METHODS: A total of 24 university medical center pathologists from eight institutions evaluated 84 colectomy specimens and 35 sets of biopsy specimens from 119 consecutive patients with colonic IBD. A specialist GI pathologist subsequently reviewed all cases without knowledge of clinical data and prior diagnosis. RESULTS: The GI pathologist's diagnoses differed from the initial diagnoses in 45% of surgical specimens and 54% of biopsy specimens. Of 70 cases initially diagnosed as UC, 30 (43%) were changed to CD or IC, whereas 4 of 23 cases (17%) initially diagnosed as CD were changed to UC or IC. The kappa coefficient for the overall agreement of initial diagnoses with the specialist GI pathologist's diagnoses was -0.01 (p = 0.98). CONCLUSIONS: There is significant interobserver variation in the histological diagnosis of colonic IBD. This may have a profound effect on clinical patient care and, especially, on the choice of operation. More accurate diagnostic criteria are needed to facilitate patient care and to optimize treatment outcome.

Use of a microsatellite marker in predicting dysplasia in ulcerative colitis.

BACKGROUND: Patients with ulcerative colitis (UC) have an increased risk of developing colorectal cancer. The current screening protocol involves an annual colonoscopy and biopsy after the patient has had the disease for 8 years. This, however, does not prevent the development of colorectal cancer. HYPOTHESIS: A microsatellite marker for IBD1 may identify individuals who are at greater risk of developing dysplasia and therefore colorectal cancer. DESIGN: Case-control study. SETTING: Single surgical practice. PATIENTS AND METHODS: DNA was extracted from peripheral leukocytes of 152 patients: 22 with UC and dysplasia; 48 with UC and no dysplasia; 24 with colorectal cancer; and 58 with noninflammatory bowel disease, nonmalignant gastrointestinal tract disease who were used as control patients. A microsatellite marker for IBD1 (D16S541) was amplified by polymerase chain reaction. Genotypes were identified using autoradiography. RESULTS: Six alleles and 15 genotypes were identified for marker D 16S541. Genotype CC was found in 33% (8/24) of cancer patients but only 12% (7/58) of controls (chi2 = 5.5; P = .02). Thirty-two percent (7/22) of patients with dysplastic UC also had this genotype, whereas only 8% (4/ 48) of patients with nondysplastic UC had the genotype (chi2 = 4.6; P = .03; vs controls: chi2 = 3.1; P = .08). CONCLUSIONS: This microsatellite marker for IBD1, when combined with other markers, has the potential to be used as a screening tool for colorectal cancer and dysplasia in patients with UC. Such a marker would be of particular use in improving the sensitivity and specificity of the current screening protocol for dysplasia and colorectal cancer for patients with UC.

Conjunctival epithelial cell hypermitosis and goblet cell hyperplasia in atopic keratoconjunctivitis.

Atopic diseases that include eczema (atopic dermatitis), asthma, and seasonal and perennial rhinoconjunctivitis are common manifestations of abnormal immediate hypersensitivity. Ocular involvement, such as atopic keratoconjunctivitis, characteristically includes conjunctival and corneal inflammation, and in a severe form, conjunctival scarring, symblepharon, corneal epitheliopathy, and visual loss. To examine the conjunctival cellular abnormalities in atopic keratoconjunctivitis, we studied the in vivo differentiation and tissue-culture growth characteristics of conjunctiva from normal subjects and patients with severe atopic keratoconjunctivitis. We examined conjunctival biopsy specimens to determine epithelial mitotic rate and goblet cell frequency, and we studied conjunctival explants to determine the latent period for fibroblast outgrowth and fibroblast doubling time. The mitotic rate for atopic keratoconjunctivitis, 6.7% +/- 2.1% (11 patients), was statistically significantly greater than for normal subjects, 2.0% +/- 0.63% (seven subjects) (P = .05). Also the goblet cell frequency for atopic keratoconjunctivitis, 14.6% +/- 3.4% (11 patients), was statistically significantly greater than for normal subjects, 4.8% +/- 0.92% (seven subjects) (P = .02). The latent period for fibroblast outgrowth and the fibroblast doubling time for atopic keratoconjunctivitis were not statistically significantly different from normal control subjects. Therefore, atopic keratoconjunctivitis was associated with conjunctival epithelial hypermitosis, goblet cell hyperplasia, and normal fibroblast tissue-culture growth. These characteristics may be useful in the diagnosis of atopic keratoconjunctivitis. We previously studied another disease characterized by chronic conjunctival inflammation and scarring, cicatricial pemphigoid, which also demonstrated conjunctival epithelial hypermitosis, but in contrast there was near absence of goblet cells, and the fibroblasts were hyperproliferative. These differences may be used to distinguish atopic keratoconjunctivitis from cicatricial pemphigoid.

Effect of caffeine on maximal strength and power in élite male athletes.

Computerized testing of 20 élite male athletes was performed to determine the effect of 7 mg kg-1 caffeine on strength and power of the knee extensors and flexors. Subjects received counterbalanced administrations of either caffeine or a placebo on two separate occasions. Peak torque (T) was measured for knee extension (ET) and flexion (FT) at angular velocities of 30 degrees, 150 degrees and 300 degrees s-1. Additionally, performance for the first 125 ms (TAE) and power (W) were recorded during 300 degrees s-1. Testing sessions were held 1 week apart, at which time the placebo/caffeine administration was reversed. A 2 x 2 repeated measures analysis of variance supplemented with a Neuman-Keuls post hoc test showed the following--significant caffeine-related increases (P < 0.05) for ET at 30 degrees s-1, ET at 300 degrees s-1, and ETAE, and EW at 300 degrees s-1. Dependent t-tests performed for pre- to post-test means showed significant changes for the caffeine group in ET at 30 degrees s-1, FT at 30 degrees s-1, FT at 150 degrees s-1, ET at 300 degrees s-1, FT at 300 degrees s-1, E and FTAE, and EW at 300 degrees s-1. No significant effects were found for the placebo trial in any variable. It was concluded that caffeine can favourably affect some strength parameters in highly resistance-trained males. However, differences in subject fibre type, motivation and caffeine sensitivity need to be elucidated.

In vivo treatment with monoclonal antibody 3.2.3 selectively eliminates natural killer cells in rats.

We recently described a mAb 3.2.3 (IgG1), that recognizes a 60-kD dimeric molecule expressed exclusively on fresh and rIL-2-activated NK cells and polymorphonuclear cells. mAb 3.2.3 enhances cytolytic activity of NK cells against selected FcR+ tumor target cells by reverse antibody-dependent cellular cytotoxicity (ADCC), indicating that it recognizes an important triggering site on NK cells. The in vivo treatment of F344 rats with mAb 3.2.3 intraperitoneally completely and selectively eliminated NK/ADCC function in the spleen and peripheral blood for up to 10 d after treatment. Total numbers and percentages of T cells, monocytes, or PMN were not decreased and T cell function, as determined by Con A stimulation, was not affected. The reduction in NK function was associated with a decrease in the numbers of LGL and the expression of other NK-related cell surface markers including CD2, CD8, and asialo GM1. Depletion of NK cells with 3.2.3 markedly decreased the survival of F344 rats injected intravenously with MADB106 mammary adenocarcinoma cells, but did not affect the subcutaneous growth of MADB106 tumors. These results indicate that mAb 3.2.3 (in contrast to anti-asialo GM1 and OX8, which are less selective markers) will be useful for studies on the functional role of NK cells in vivo as well as their in vivo differentiation and origin from 3.2.3- precursors.

Reduced natural killer cell activity in patients with systemic sclerosis. Correlation with clinical disease type.

Natural killer (NK) cell number and function were determined in 69 systemic sclerosis (SSc) patients (41 with diffuse cutaneous SSc, 24 with limited cutaneous SSc, and 4 with scleroderma in an overlap syndrome). The results were compared with those obtained from 5 patients with Raynaud's disease and from 27 normal controls. Natural and antibody-dependent killing was reduced in the total group of SSc patients compared with controls, but these differences were primarily attributable to patients with the diffuse form of the disease who were seen early in their illness (less than 5 years after onset). NK cell numbers were not significantly reduced in patients compared with controls, although lower numbers were observed in individuals with early diffuse disease. Other clinical parameters, such as treatment with D-penicillamine or the presence of scleroderma-specific autoantibodies, did not exert an independent effect on NK cell function. These findings suggest a possible central role for NK cells in the pathogenesis of SSc.

Mother-infant separation in group-living rhesus macaques: a hormonal analysis.

Adrenocortical responsiveness to separation in group-living rhesus macaque mother-infant pairs was determined. Cortisol evaluations were complemented by behavioral observations of mother-infant interactions and group social behavior. Infants, but not their mothers, showed cortisol elevations that could be attributed specifically to separation. Steroid-behavior relationships suggested that the infants of high dominant mothers evinced the greatest adrenocortical response to separation. These data exemplify the complexities involved in determining endocrine/behavior relationships in a group-living situation.

Nutritional variables and their effect on the development of ultrasonic vocalizations in rat pups.

Measures of ultrasonic vocalizations were made on alternate days during the first and second weeks postpartum in rat pups reared by mothers fed either control (23%) or low protein (8%) diets. Compared to those reared by control mothers, pups reared by low protein mothers emitted significantly fewer ultrasonic vocalizations. The hypothesis that malnutrition might shift the age at which peak rate of vocalizations were emitted was not confirmed.