Effect of interleukin 2 on Kupffer cell activation. Interleukin 2 primes and activates Kupffer cells to suppress hepatocyte protein synthesis in vitro

Interleukin 2 (IL-2) is an essential mediator of the immune response and has also been shown to be protective in experimental models of sepsis. Macrophages have IL-2 receptors but their function is unknown. We investigated the effect of IL-2 on Kupffer cells, the fixed macrophages of the liver, using an in vitro rat hepatocyte-Kupffer cell coculture system. In this model, endotoxin (lipopolysaccharide) triggers Kupffer cells to induce suppression of hepatocyte protein synthesis. We found that pretreatment with 10 U/mL or more of IL-2 primed Kupffer cells, significantly reducing the concentration of lipopolysaccharide necessary to trigger Kupffer cell-mediated suppression of hepatocyte protein synthesis. Higher concentrations of IL-2 (greater than or equal to 1 x 10(4) U/mL) alone were capable of priming and triggering Kupffer cells to suppress hepatocyte protein synthesis. These data show that IL-2 increases Kupffer cell sensitivity to endotoxin, suggesting that IL-2 may play an important role in regulating macrophage responses to septic stimuli.     

Dermatologic adverse drug reactions in a family medicine setting.

To determine the prevalence of dermatologic adverse drug reactions in a family medicine outpatient practice setting, identify associated drug classes, and describe associated patient demographics and risk factors, we reviewed the charts of 557 patients in a university-based family medicine center who were diagnosed with a dermatologic condition. The study population included all patients diagnosed during a 1-year period. Thirty-five patients (6.3%) were identified as having dermatologic adverse drug reactions, of which the two most common types were exanthematous eruptions (n = 18 [51.4%]) and generalized erythroderma (n = 6 [17.1%]), with antibiotic use accounting for the majority (n = 21 [60.0%]) of reactions. Patient characteristics most commonly associated with a dermatologic adverse drug reaction were race (African-American), gender (female), and age (70 years and older). These data should provide insight into the types of cutaneous drug reactions commonly seen in community practice. Educational programs in all health-care disciplines, particularly medicine, pharmacy, and public health, that incorporate pharmacoepidemiologic strategies into their curricula are necessary to improve the overall process of monitoring and reporting of adverse drug reactions.     

Improved quality-control detection of false-negative Pap smears using the Autopap 300 QC system

Federally-mandated quality control (QC) in Papanicolaou (Pap) smear testing requires rescreening of 10% of negative smears, to include cases selected randomly as well as smears from patients that may have a higher risk for developing cervical cancer based on clinical information. FDA approval of NeoPath's AutoPap 300 QC system (NeoPath, Inc., Redmond, WA) allows practical QC rescreening of all negatives. We tested the ability of AutoPap to help increase identification of detection errors compared to random 10%/high-risk selection. From March 1-August 30, 1997, we utilized AutoPap/high-risk status to select cases for manual rescreen, and compared the rate of identification of primary screening errors to that for the preceding year using 10% random selection/high-risk status. Of 35,027 smears accessioned, 31,240 (89.1%) were screened as negative and 7,965 were selected for manual rescreen. Of these, 353 were determined to be abnormal. Most abnormals identified by this protocol were classified as atypical squamous or glandular cells of undetermined significance (ASCUS or AGUS). However, 59 low-grade squamous intraepithelial lesions (LSIL) and 13 high-grade squamous intraepithelial lesions (HSIL), many with few abnormal cells, were also identified. These results represented an increase in pickup rate of false negative due to detection errors of 2.3-, 2.8- and 5.6-fold for atypical squamous or glandular cells of undetermined significance, LSIL, and HSIL, respectively, when accounting for the volume differences over the time period measured. Our findings strongly support the conclusions drawn from clinical trials of the AutoPap that false negatives due to detection error can be significantly reduced when using AutoPap as part of a routine quality control program.     

Primary gastric apoptosis-rich T-cell lymphoma co-expressing CD4, CD8, and cytotoxic molecules

In contrast to primary gastric lymphomas of B-cell type, little is known about primary gastric T-cell lymphomas. We describe three cases with remarkably similar features: diffuse growth, epitheliotropism, medium too large cell size, high apoptotic rates, and a CD3+, CD4+, CD8+, CD45RO+ immunophenotype. Clonal TCRγ gene rearrangement was shown in two cases. Epstein-Barr virus infection was excluded in two cases. Taking advantage of fresh-frozen material, we analyzed two cases further, revealing CD5–, CD16+, CD56–, CD57–, CD25+, CD30+, CD103 (αEβ7)+, bcl-2 protein+, CD95+, CD95 ligand(L)–. CD95L, however, was detected in histiocytic and fibroblastoid by stander cells. The lymphomas expressed granzyme B, perforin, and the TIA-1 antigen in various combinations. All three cases had a very unfavorable clinical course characterized by local recurrence and/or dissemination to other epithelial sites, leading to death within 6–12 months after the initial diagnosis despite surgery and aggressive antineoplastic treatment. These data suggest a novel variant of peripheral T-cell lymphoma operationally characterized as primary gastric, apoptosis-rich, CD103+, EBV-, T-cell lymphoma co-expressing CD4, CD8, CD16 and cytotoxic molecules. Received: 20 August 1999 / Accepted: 2 November 1999     

Comparison of four methods for identification of gram-negative non-fermenters: Organisms less commonly encountered in clinical specimens

Four commercial kits - Oxi/Ferm (OF), API 20E (AP), Minitek (MT), Flow N/F (NF) were evaluated, without additional tests, for identification of 105 opportunistic Gram-negative non-fermentative rods. OF correctly identified 42% of strains, with 35% as part (but not first) of a spectrum of identifications (SI) and 23% incorrect identification. MT yielded 75% correct identification, with 12% SI and 13% incorrect. AP correctly identified 64% of strains, with 26% SI, 10% incorrect. NF correctly speciated 70% of strains, with 24% SI, 6% incorrect. All 4 methods show deficiencies in identification of these rare but increasingly clinically encountered organisms. Addition of new tests/modification of existing ones would render these systems more capable of identifying this organisms group.     

An estrogen metabolism-related polymorphism of the 17-alpha HSD gene is associated with perimenopausal body mass index

In a cross-sectional study of 2,802 perimenopausal caucasian women, carriage of at least one mutated allele of the 17-alpha-hydroxysteroid dehydrogenase type 1 (17-alpha HSD) vlV A-->C single nucleotide polymorphism (SNP) was associated with a significantly increased body mass index (mean 24.3 +/- 4.4 kg/m(2) vs. 23.5 +/- 4.2 kg/m(2); P<.001), and obesity was more frequent among mutant allele carriers (P=.06; odds ratio 1.38; 95% confidence interval 0.97-1.95), providing evidence of 17-alpha HSD as a candidate gene of perimenopausal obesity.     

A polymorphism of the interleukin-1 beta gene is associated with sperm pathology in humans

In a prospective case-control study of 127 normozoospermic and 435 non-normozoospermic Caucasian men, the genotype frequencies of a polymorphism of the interleukin-1 beta gene (IL-1beta Taq C-->T) were statistically significantly different between groups (homozygous wild-type C/C [57%], heterozygous C/T [42%], and homozygous mutant T/T [1%] vs. C/C [57%], C/T [36%], T/T [7%] for normozoospermic and non-normozoospermic men, respectively; odds ratio, 4.8; 95% confidence interval, 1.13 to 20.28). This association was restricted to men with the oligoasthenoteratozoospermia (OAT) syndrome. We conclude that the investigated polymorphism is associated with sperm pathology in Caucasians.     

Treatment of oropharyngeal squamous cell carcinoma with external beam radiation combined with interstitial brachytherapy

BACKGROUND: We reviewed the outcomes of oropharyngeal squamous cell carcinoma treated with external beam radiation and interstitial brachytherapy. METHODS: Ninety patients with squamous cell carcinoma of the oropharynx were treated with interstitial brachytherapy at the University of Utah between 1984 and 2001. Seventy-two patients received external beam radiotherapy (EBRT) followed by brachytherapy boost, 11 had surgery followed by EBRT and brachytherapy, 4 had surgery and brachytherapy, and 3 were treated with brachytherapy alone. Median doses for EBRT and brachytherapy were 50 and 24 Gy, respectively. RESULTS: Median follow-up after brachytherapy was 48.3 months for all patients. Five-year local control, disease-free survival, and overall survival were 76%, 61%, and 55%. For T1, T2, T3, and T4, 5-year local control rates were 83%, 79%, 79%, and 64%, respectively. Severe complications occurred in 13 patients, including 2 treatment-related deaths. CONCLUSIONS: EBRT combined with interstitial brachytherapy provide good local control rates for locally advanced oropharyngeal squamous cell carcinoma.