Extraperitoneal endometriosis: a diagnosis to be considered

Summary BACKGROUND: Endometriosis is a relatively common pathology in women of childbearing age and of low parity but rarely shows extraperitoneal involvement. The main aim of this paper is to raise the attention of specialists to the necessity of carrying out penetrating diagnosis of nonspecific extraperitoneal masses occurring in women of reproductive age. METHODS: We performed a retrospective review of six patients diagnosed with extraperitoneal endometriosis who were treated at the Vega Baja University Hospital (Spain) during the last 5 years. RESULTS: Surgical treatment had positive results in five patients. The preoperative diagnosis was correctly made in only two patients. The accurate aetiology of endometriosis remains unknown and diagnosis is based on clinical and cytopathological findings. CONCLUSIONS: Surgical treatment of extraperitoneal endometriosis is recommended. However, postoperative follow-up is obligatory and hormonal suppressive therapy may be necessary. Medical treatment with gestagens, Danazol, or agonists of the gonadotropin-releasing hormone are ineffective in endometriomas which are bigger than 2 cm.      

Effects of the antimigraine compound zolmitriptan ('Zomig') on psychomotor performance alone and in combination with diazepam in healthy volunteers

Zolmitriptan (Zomig^TM) is a 5HT_1B/1D agonist which has the ability to cross the intact blood-brain barrier to access central as well as peripheral receptors. Because of the potential for central nervous system side effects, this randomized, double-blind, placebo-controlled, 6-period crossover study evaluated the effects of 2.5 and 5 mg doses of zolmitriptan on psychomotor performance and investigated any pharmacodynamic or pharmacokinetic interaction with diazepam. Twelve healthy volunteers received the following "treatments" as single doses: zolmitriptan 2.5 mg, zolmitriptan 5 mg, diazepam 10 mg, zolmitriptan 2.5 mg+diazepam 10 mg, zolmitriptan 5 mg+diazepam 10 mg and placebo. Pre-dose and at 1, 4, 8, and 24 h post-dose, the following validated battery of psychomotor tests was performed: Bond-Lader visual analogue scales (calmness, contentedness, and alertness factors), critical flicker fusion test, choice reaction time (recognition, motor, and total reaction times), finger-tapping test, number cancellation test and digit symbol substitution test. Plasma concentrations of zolmitriptan, its active metabolite, and diazepam and its active metabolites were measured at the same timepoints. Zolmitriptan 2.5 and 5 mg had no effect on psychomotor function when given alone. In contrast, diazepam 10 mg had profound effects, consistent with its sedative properties, but there was no synergism on concomitant administration of either dose of zolmitriptan. Plasma concentrations of zolmitriptan, diazepam, and their respective active metabolites were similar when the two drugs were given alone or in combination.     

Indapamide inhibits endothelium-dependent contractions in the aorta of the spontaneously hypertensive rat

Summary— Experiments were designed to determine whether or not indapamide, an antihypertensive agent with vasodilator properties, inhibits endothelium-dependent contractions. Rings of aortae with and without endothelium from spontaneously hypertensive rats (SHR) were suspended in conventional organ chambers for the measurement of isometric force. Acetylcholine and adenosine diphosphate-β-S in the presence of a nitric oxide synthase inhibitor, caused endothelium-dependent contractions, which were inhibited by indapamide. The compound (10⁻⁴M) also slightly reduced the contractions of rings without endothelium evoked by U-46,619, which activates thromboxane-endoperoxide receptors. These results demonstrate that indapamide inhibits endothelium-dependent contractions in the SHR aorta, and suggest that the inhibition is due, at least in part, to the action of the drug on the hypertensive vascular smooth muscle.     

Redefining the significance of aneuploidy in the prognostic assessment of colorectal cancer

The aberrant content of DNA, or aneuploidy, is a hallmark of tumor cells and may be associated with malignant potential. Based on the hypothesis that aneuploidy, as a form of genetic instability, results in an increased capability to generate cell heterogeneity, we investigated whether a comprehensive assessment of aneuploidy extent and degree might be a reliable indicator of tumor aggressiveness. DNA content was determined by flow cytometry in the infiltrating front of 131 paraffin-embedded primary colorectal carcinomas collected in a prospective design. Enrichment of tumor cells by sample microdissection resulted in neoplastic cell contents above 75%. An estimate of aneuploidy, the aneuploidy index (AI), was calculated as the tumor DNA content adjusted by the percentage of diploid and aneuploid cells in G0/G1. Thirty-nine tumors were diploid, 90 hyperdiploid, and 2 hypodiploid. The mean AI in aneuploid tumors was 1.20+/-0.17 and correlated with Dukes' stage and metastasis (p < 0.05). A high AI (receiver operating characteristic curve cutoff value greater than 1.14) predicted a poorer outcome in univariate (p = 0.004) and multivariate (p = 0.01) analyses. Based on these results, we postulate that aneuploidy is the molecular engine of progression in a subset of colorectal cancers, in which the AI seems to be a sensible and independent gauge of malignant potential. The AI determination may have prognostic application in colorectal cancer, especially in low-grade tumors, which might benefit from coadjuvant therapies.     

Needle biopsy of renal allografts: comparison of two techniques

Two techniques for renal allograft biopsy were retrospectively evaluated to compare relative safety and efficacy. After ultrasound (US) localization of the kidney and biopsy with a hand-held 14-gauge cutting needle, an adequate specimen was obtained in 74 of 77 cases (96%). Major complications occurred in six of these 77 cases (8%). One hundred four biopsies were performed by using a smaller 18-gauge cutting needle with a spring-loaded biopsy "gun" and real-time US guidance. With this newer technique, specimens adequate for diagnosis were obtained in 99 biopsies (95%). There was a single major complication with this technique (1%). The 18-gauge needle with real-time US guidance yields comparably adequate specimens with a lower frequency of complications.     

Synovialisation of the torn anterior cruciate ligament of the knee: comparison between magnetic resonance and arthroscopy

The aim of this study was to assess the accuracy of MR in the diagnosis of synovialisation of the anterior cruciate ligament (ACL) compared with arthroscopy. One hundred and forty-nine patients were examined with MR imaging and arthroscopy of the knee. The MR sign used to consider a synovialised ACL consisted of hypointense fibrillar tracts, disrupted and wavily, in its expected course. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV), comparison of proportions (McNemar test) and Kappa values for agreement between MR imaging and arthroscopy were calculated. Of the 133 (89.3 %) ligaments without synovialisation at arthroscopy, 130 accorded with the MR results. Of the 16 (10.7 %) synovialised ligaments, 13 accorded with the MR results. Three false-positive and three false-negative MR diagnoses were identified. The agreement between both techniques was excellent (Kappa = 0.79; p = 0.000), without differences (McNemar test; p = 1). Sensitivity was 0.81, specificity 0.98, PPV 0.98 and NPV 0.81. Magnetic resonance imaging is highly reliability for synovialisation diagnosis. The imaging sign used to diagnose synovialised ACL (hypointense comma-like tracts in its expected course) is reliable. As this reparative process can simulate an intact ligament, knowledge of this sign is important in diagnosing synovialisation of ACL tears so as not to confuse it with normal ACL. Received: 17 June 1998; Accepted: 6 August 1998     

Preoperative uracil, tegafur, and concomitant radiotherapy in operable rectal cancer: a phase II multicenter study with 3 years' follow-Up.

PURPOSE: To assess tolerance and efficacy of preoperative treatment with uracil/tegafur and radiotherapy (RT) followed by surgery and postoperative flurouracil (FU)/leucovorin (LV) in patients with rectal cancer. PATIENTS AND METHODS: Patients (n = 94) with potentially resectable tumors, ultrasound at stages T2N+ (n = 4), T3 (n = 77), T4 (n = 13) were treated with UFT (400 mg/m2/d, 5 days a week for 5 weeks) and concomitant RT to the pelvis (45 Gy; 1.8 Gy/d over 5 weeks). Patients underwent surgery 5 to 6 weeks later followed by four cycles of FU/LV. Primary end points included downstaging, pathologic responses, and sphincter-preserving surgery. Secondary end points were recurrence-free survival and overall survival. RESULTS: All patients received the full RT dose. Fifteen patients (16%) needed UFT dose reduction. Preoperative G3+ toxicities included diarrhea (14%), leukopenia (1%), thrombocytopenia (1%), and nausea (4%). The downstaging rate was 54%, pathologic complete response (pCR) was 9% and, in an additional 23%, there were only residual microscopic foci. When cellular viability criteria were taken into account, the pCR was 15%. From 43 patients with abdominoperineal resection indication, 11 (25%) had sphincter-preserving surgery performed. Postoperative scheduled chemotherapy dose was not administered to 24% of patients because of G3+ toxicity (diarrhea, 8%; mucositis, 9%; and leukopenia, 7%). Patients with downstaging had significantly higher survival and recurrence-free survival rates than those without. At 3 years, actuarial patterns of failure were pelvic, 5% and distant, 11%. OS was 75%. CONCLUSION: UFT combined with RT is safe and effective. In resectable rectal cancer, if preoperative treatment is considered, this approach can be an option.     

Pharmacokinetics and protein binding of intravenous ibuprofen in the premature newborn infant

The elimination, disposition and protein binding of ibuprofen (IBU) in premature infants were studied for use in the prevention of intraventricular hemorrhage and closure of patent ductus arteriosus. The kinetic profile of i.v. IBU lysine (10 mg/kg bolus) given within the first 3 h after birth was studied in 21 premature neonates (mean birthweight = 944.7 g, range: 575–1450 g; gestational age: 26.8 weeks, range: 22–31 weeks). Blood samples (0.3 ml/sample) were obtained at time 0 and at 1, 3, 6, 12, 24, 48, and 72 h post-dose for IBU by high-performance liquid chromatography (HPLC). Kinetic analyses assumed applicability of one open-compartment model and calculations from the model-independent areas under the time concentration curve (AUC). Data (mean ± SEM) show that apparent volume of distribution (AVd) was 62.1 ± 3.9 ml/kg, plasma t _1/2 beta was 30.5 ± 4.2 h, elimination rate constant (k_el) was 0.032 ± 0.004 h^-1plasma clearance was 2.06 ± 0.33 ml/kg/h and plasma concentration (Cp) at 1 h was 180.6 ±11.1 mg/1. Gestational age and birthweight were not related to drug elimination. In 10 neonates, IBU maintenance dose of 5 mg/kg once daily on days 2 and 3 generated mean Cp of 116.6 ± 54.5 mg/1 and 113.6 ± 58.2mg/1, respectively. Protein binding by ultrafiltration and capillary electrophoresis showed that the percentage bound IBU was significantly lower in full term cord plasma (94.98 ± 0.39%, n = 26) compared to adult plasma protein (mean ± SE = 98.73 ± 0.31%, n = 8, p < 0.0001). Compared to data from adults and older children, IBU elimination is markedly prolonged in neonates and protein binding is slightly lower. Thus, investigational and clinical therapeutic regimens should be adjusted to account for decreased drug disposition to ensure safe and effective therapy.