Serum interleukin-4 is elevated in clinical drug-induced liver injury.

BACKGROUND: Drug-induced liver injury (DILI) remains a challenging diagnosis due to an absence of specific biomarkers. DILI due to volatile anaesthetics (VA-DILI) is characterised by trifluoroacetyl and CYP2E1 antibodies, but may not be seen for weeks after injury. Interleukin-4 (IL-4) may be involved in the production of these antibodies and may serve as a clinically useful early biomarker of VA-DILI. AIM: To prospectively compare serum IL-4 levels between patients who develop VA-DILI and controls following exposure to the volatile anaesthetic. METHODS: A nested case-control study of patients exposed to VA during surgery was conducted. Thirteen DILI cases were identified from the original cohort, and 26 controls were matched according to age, sex and VA agent. Serum samples were collected before and 48-96 h after VA exposure, and analysed for IL-4 using quantitative enzyme-linked immunosorbent assay techniques. RESULTS: There was a statistically significant difference in serum IL-4 in post-VA samples between DILI cases and controls (control: 0.030 pg/mL, IQR: 0.030 - 0.030 pg/mL vs DILI: 0.044 pg/mL, IQR: 0.030 - 0.061 pg/mL; p = 0.039). A greater proportion of DILI cases had post-VA IL-4 levels above the assay lower limit of detection compared to controls (control: 23% vs DILI: 69%; p = 0.013). CONCLUSION: IL-4 is a potential biomarker of DILI. Clinical diagnosis and understanding of DILI disease mechanisms may be improved by further investigation of novel biomarkers, and this IL-4 signal in serum is important as proof of concept for prospective study designs.

[Stromal uterine sarcoma arising from intestinal endometriosis after abdominal hysterectomy and salpingo-oophorectomy].

The incidence of ectopic endometriosis is 4% to 18%. The intestinal type is quite common with the rectosigmoid the most likely part of the bowel to be involved due to its pelvic location. A 43-year-old woman, whose symptoms, X-ray and endoscopic findings suggested malignancy of the rectosigmoid, is presented. Primary malignancy of the bowel was excluded by endoscopic biopsies. Histological examination at operation showed stromal sarcoma of the uterus with foci of endometriosis. There is no report in the English literature of transformation of intestinal endometriosis into malignancy, such as stromal sarcoma of the uterus, which imitates a primary malignancy with obstruction of the rectosigmoid.

Gallbladder contraction in familial dysautonomia.

The impaired function of the autonomic nervous system in patients with familial dysautonomia (FD) is frequently associated with gastrointestinal dysfunction. This study sought to determine whether gallbladder contraction is also affected in these patients. Nine consecutive patients with FD were assessed by real-time ultrasonography for gallbladder volume and calculated percentage of gallbladder contraction before and 45-60 min after a 50 g fatty meal, and compared with nine healthy control patients, matched for age and gender. Gallbladder volume before the fatty meal was found to be larger in healthy controls than in FD patients (25.4+/-9.5 and 15.4+/-7.4 ml3, respectively; p = 0.024). No significant difference was demonstrated between the groups after the fatty meal (controls: 12.1+/-6.0; FD: 9.0+/-6.6 ml, respectively) and the calculated percentage of gallbladder contraction was similar in both groups (controls: 53.4+/-16.6; FD: 44.8+/-18.8%). These results indicate that gallbladder function in FD patients does not differ from the general population and preventive measures for gallstone formation are not required.

Effects of serotonin on intracellular pH and contraction in vascular smooth muscle.

Serotonin (5-HT) and other contractile agonists stimulate Na(+)-H+ exchange in vascular smooth muscle. Since intracellular alkalinization, per se, stimulates contraction, we tested whether 5-HT-induced contraction was associated with an increased pHi. In HCO3(-)-free buffer (pHo 7.4), 5-HT (10(-5) M) increased pHi, as measured by 2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein fluorescence, from 7.10 +/- 0.03 to 7.34 +/- 0.03 (p < 0.01) in primary cultures of canine femoral artery vascular smooth muscle cells grown to confluence in the presence of 10% fetal calf serum. In HCO3- buffer (24 mM, pHo 7.4), resting pHi was 7.26 +/- 0.04 (p < 0.01 versus HCO3(-)-free buffer) but was not altered by 5-HT. In both types of buffer, 5-HT stimulated 5-(N-ethyl-N-isopropyl)amiloride-sensitive 22Na+ uptake (Na(+)-H+ exchange). In HCO3- buffer and in Na(+)- and HCO3(-)-free buffer, 5-HT increased 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid-sensitive 36Cl- uptake, suggesting that 5-HT stimulated Na(+)-independent Cl(-)-HCO3- and Cl(-)-Cl- exchange activities, respectively. Individual vascular smooth muscle cells were then cultured on rat tail tendon collagen gels in the presence of 0.5% fetal calf serum, and cell length and pHi were measured by video and epifluorescence microscopy. 5-HT contracted cells in a dose-dependent, reversible, and ketanserin-inhibitable manner. These cells, like cells grown in 10% fetal calf serum, exhibited Na(+)-H+ and Na(+)-independent Cl(-)-HCO3- exchange. In HCO3- buffer, 5-HT contracted cells without an associated change in pHi. We concluded the following: 1) 5-HT stimulated both Na(+)-H+ and Na(+)-independent Cl(-)-HCO3- exchange activities in cultured vascular smooth muscle cells in parallel. 2) As a result of enhanced H+ and HCO3- efflux, pHi was not altered. 3) In the presence of HCO3-, 5-HT-induced contraction was not associated with a change in pHi.