[The contribution of capsule endoscopy to the diagnosis of small-bowel tumors in cases of obscure overt gastrointestinal bleeding].

BACKGROUND: The source of obscure bleeding is usually located in the small bowel. The use of capsule endoscopy (CE) has changed the management of these patients. GOALS: To review our experience with the diagnosis of small bowel tumors by CE in patients with obscure overt gastrointestinal bleeding. METHODS: Retrospective analysis of CE examinations performed consecutively in two university-affiliated hospitals. RESULTS: Among 156 patients who underwent CE examination (including 58 patients with obscure overt bleeding), five patients, all of whom presented with melena, were diagnosed as having a small bowel tumor. Three tumors were found in one patient (two ileal carcinoids and one ileal benign stromal tumor). A jejunal benign stromal tumor was diagnosed in two other patients by push enteroscopy. One of these was missed by a subsequent capsule endoscopy examination, and in the other, only active bleeding was detected by prior capsule endoscopy. In two patients, three small tumors were detected, beyond the reach of push enteroscopy, but surgical confirmation was not available. No tumors were found among patients in whom the indication for CE examination was not obscure overt bleeding. CONCLUSIONS: The possibility of finding a small bowel tumor emphasizes the role of capsule endoscopy in patients with obscure overt gastrointestinal bleeding. Push enteroscopy should be performed when capsule endoscopy yields negative or only suspicious findings.

Properties of microsomal delta4-3-ketosteroid 5alpha-reductase in immature rat ovary. Inhibition by estradiol-17beta.

The subcellular distribution of immature rat ovarian 5alpha-reductase has been studied by utilizing 20alpha-hydroxypregn-4-en-3-one as substrate. The main enzyme activity was found to be associated with the microsomal fraction, with lower activities in the 1000 X g and 10 000 X g fractions. The enzyme activity associated with the microsomes exhibited an apparent Km of 3.0 +/- 1.1 micrometer for 20alpha-hydroxypregn-4-en-3-one and 36.3 +/- 6.7 micrometer for testosterone as substrate. Progesterone and testosterone competitively inhibited the 5alpha-reduction of 20alpha-hydroxypregn-4-en-3-one; estradiol-17beta was found to be a noncompetitive inhibitor of this reaction. A concentration of estradiol-17beta as low as 1 micrometer when added to 25 micrometer concentration of 20alpha-hydroxypregn-4-en-3-one exerted a significant inhibition of 5alpha-reductase activity.

Synthesis of A/B-ring partial analogs of bruceantin as potential antimalarial agents.

Bruceantin (1), a classical quassinoid with the highest reported antimalarial activity among the quassinoids examined thus far, was selected as a natural product lead for the design of a series of A/B-ring analogs. A viable strategy for the synthesis of the series was developed. The functionalized A-ring and the C-15 ester moiety in bruceantin are incorporated in all designed compounds. The preliminary bioassay results will be discussed in detail.

Effect of human chorionic gonadotropin and prolactin on 20 alpha-hydroxysteroid dehydrogenase activity in granulosa cells of immature rat ovary.

The effects of FSH, hCG, and PRL on the activity of 20 alpha-hydroxysteroid dehydrogenase (20 alpha-SDH) of separate ovarian components of hypophysectomized, diethylstilbestrol-treated rats were studied. Enzyme activity was found to reside mainly in granulosa cells. FSH induced an increase in enzyme activity. A preparation of FSH was purified by adsorbing its LH contamination on rat corpora lutea membranes and by further neutralizing LH traces with an antiserum to the beta-subunit of LH. This purified FSH retained the ability to induce a 6-fold increase in specific enzyme activity in granulosa cells of hypophysectomized, diethylstilbestrol-treated rats. Administration of hCG to rats treated with purified FSH, further enhanced 20 alpha-SDH activity in granulosa cells up to 11.5-fold above control. PRL, which is known to inhibit 20 alpha-SDH activity in regressing rat corpora lutea, suppressed the FSH-induced increase in enzyme activity in the granulosa cells.

Decrease in blood and ovarian 3 alpha- and 3 beta-androstanediol levels in rats induced to ovulate with pregnant mare serum gonadotropin.

Several hours before the first ovulation progesterone metabolism in the rat ovary, in vitro, is shifted from the production of 5 alpha-androstane-3 alpha, 17 beta-diol (3 alpha-diol) as the major metabolite toward the production of 4-ene-3-oxosteroids. In the present paper, changes in levels of 3 alpha-diol and its 3 beta-epimer as well as testosterone in blood and ovaries around the time of the first ovulation have been studied in immature PMSG-treated rats. Forty-eight hours after PMSG, a considerable increase in blood and ovarian testosterone concentration was observed, whereas the concentrations of both androstanediols in blood decreased sharply. At 52 h, the level of ovarian 3 beta-diol was only one third of the control level and continued to fall. The decrease in ovarian 3 alpha-diol was less pronounced, but reached about half, or less, of the control value. In PMSG-treated rats in which the LH surge was blocked by pentobarbitone, the decrease in blood diols was delayed but not prevented. It is concluded that the decrease in production of the androstanediols preceding the first ovulation observed previously in isolated ovaries, also occurs in the intact rat. The decrease in androstanediols occurs very shortly before an ovulation induced with an injection of PMSG and is dependent on the occurrence of an LH surge. Since it is assumed that the androstanediols have a prepubertal role in inhibiting uterine and ovarian growth and in preventing cyclic LH release, it is essential that their concentration decrease several hours before the first ovulation.

A specific FSH receptor in rat granulosa cells: properties of binding in vitro.

The specific binding of [125I]iodoFSH to granulosa cells collected from immature, hypophysectomized, DES-treated rats, was studied in vitro. Specific binding occurred after 5 min and reached maximum after 3 h of incubation at 37 C. Non specific binding was very low (less than 10% of the total binding). The [25I]iodoFSH remained tightly associated with the receptor at pH 7.5, but was rapidly dissociated at pH 5. Unlabeled hFSH competitively inhibited [125I]iodoFSH binding. Kinetic analyses of equilibrium binding experiments gave an apparent association constant (Ka) of 1.34 (+/- 0.31) x 10(10)M-1 [mean (+/- SE)] and a number of binding sites per cell of (NB) 1, 130 +/- 70 (mean +/- SE). Rat prolactin, wheat germ agglutinin, and concanavalin-A did not compete with [125I]iodoFSH, but hLH, hCG, and rTSH competed at doses 300- to 900-fold higher than those of hFSH. Granulosa cells isolated from adult DES-treated rats, as well as cells collected from medium and preovulatory follicles of proestrous rats, gave Ka and NB values similar to those described above. A comparative study of rabbit granulosa cells indicated a much lower binding affinity compared with those from the rat.

Stimulation of creatine kinase activity in rat organs by human growth hormone in vivo and in vitro.

Intraperitoneal injection of human GH (hGH) (4 micrograms/g BW) into 21-day-old rats causes, 24 h later, an increase in creatine kinase (CK) specific activity in kidney (1.7-fold), liver (1.6-fold), and in epiphyseal cartilage (1.8-fold). Similar stimulation was obtained when tissue explants were incubated for 24 h with hGH (1 microgram/ml); CK activity rose 1.8-fold in kidney, 1.9-fold in the liver, and 2.6-fold in epiphyseal cartilage. Highly significant stimulation of CK specific activity was obtained in these same organs in hypophysectomized rats. The increase in CK specific activity in the kidney, to some extent in the liver, but not in the epiphyseal cartilage, was also obtained on in vivo treatment with either human placental lactogen or ovine PRL. Stimulation of CK in these three organs by hGH is followed by a parallel increase in DNA synthesis. Dexamethasone, which was also found to increase CK activity in rat kidney and liver, did not affect the increase of CK by hGH in the kidney, stimulated the effect of hGH in the liver, and partially inhibited the effect of hGH in the epiphyseal cartilage. Diethylaminoethyl cellulose chromatography revealed that the basal and induced activity of CK in all cases was due to the brain type isozyme. On the basis of this evidence for a direct effect of hGH on CK brain type activity, we suggest that its stimulation is potentially a convenient and sensitive assay for biological activity of GH.

Aromatization of androgens by human abdominal and breast fat tissue.

The ability of human abdominal, breast and axillary fat to convert androgens into estrogens was investigated by incubating labeled substrates in the presence of NADPH with a variety of cell preparations. The incubation products were subjected to phenolic partition, paper chromatography, methyl-ether formation, repeat chromatography and crystallization with cold carrier reference standards to constant specific activity. Androstenedione was converted to estrone and, to a lesser extent, to 17beta-estradiol by crude homogenates, minces, fat-free particulate fractions (1,000-100,000 time g) and isolated fat cells obtained from abdominal, breast or axillary fat. Testosterone was found to be aromatized as actively as androstenedione, but inthis case more 17 beta-estrodiol was formed than estrone. 19-Hydroxyandrostenedione-2 also served as substrate, givingresults similar to those obtained with androstenedione. Fat tissue obtained from cancerous breasts was found to be as active as normal breast fat (1-4 pg/g fat/90 min) and within the range found for abdominal fat (1-27 pg/g fat/90 min). In each case in which axillary fat was compared to breast fat from the same subject, the activity of the axillary fat was 5 to 10 times higher. The results indicate a possible role of adipose tissue as a significant extra-gonadal source of estrogens.

Cellular and secretory mechanisms related to delayed radiation-induced microvessel dysfunction in the spinal cord of rats.

PURPOSE: This study aimed to investigate long-term, radiation-induced changes in microvessel permeability, the profile of the vasoactive mediators endothelin and nitric oxide, and the response of specific cell systems in the irradiated spinal cord of rats. METHODS AND MATERIALS: The thoracolumbar spinal cords of Fischer rats were irradiated to a dose of 15 Gy, and the rats were sacrificed at various times afterward. Endothelin levels and nitric oxide-synthase (NOS) activity were assayed in extracts of spinal cords. Microvascular permeability and the effect of treatment with recombinant human manganese superoxide dismutase (r-hMnSOD) were assessed quantitatively. Immunohistochemistry evaluated astrocytes, microglia, vascular basal membrane, and neurofilaments. RESULTS: None of the rats developed neurologic dysfunction. Endothelin levels were significantly reduced at 18 h after irradiation and markedly attenuated after 10 days (p < 0.007). Thereafter, endothelin levels returned to normal values at 56 days after radiation and escalated to markedly high levels after 120 and 180 days (p < 0.002). NOS activity remained very low throughout the period of follow-up and failed to counterbalance the shifts in endothelin levels. Treatment with r-hMnSOD had no effect on normal vascular permeability but it abolished the abnormally increased permeability measured at 18 h after radiation and again after 120 and 180 days. Standard microscopic evaluation failed to reveal abnormalities in the irradiated spinal cord, but immunohistochemical staining showed a progressive increase in the number of microglial cells per field after 120 and 180 days (p < 0003). A similar increase in the number of astrocytic cells per field was noted after more than 180 days, but an earlier short lasting peak was also noted at 14 days after radiation. No abnormalities were found in blood vessel configuration, density, diameter, and basal membrane staining, or in the neurofilaments. CONCLUSION: Marked imbalance in the regulatory function of endothelium-derived mediators of the vascular tone is present after radiation therapy probably inducing chronic vasoconstriction. This imbalance favors localized procoagulation that may enhance the consequent loss of function measured as increased permeability. Microglial proliferation may account for continuous release of superoxide that may enhance disruption of normal permeability. The latter is corrected by SOD treatment. Astrocytic proliferation may present a response to the mitogenic effect of endothelin and to microglial-derived paracrine effect of cytokines.

Successful treatment of radiation-induced fibrosis using Cu/Zn-SOD and Mn-SOD: an experimental study.

PURPOSE: To establish how far liposomal copper/zinc superoxide dismutase (Cu/Zn-SOD) and manganese superoxide dismutase (Mn-SOD), respectively, reduce radiation-induced fibrosis (RIF), using a well-characterized pig model of RIF permitting the design of a controlled laboratory experiment. METHODS AND MATERIALS: In this model of acute localized gamma irradiation simulating accidental overexposure in humans, three groups of five large white pigs were irradiated using a collimated 192Ir source to deliver a single dose of 160 Gy onto the skin surface (100%) of the outer side of the thigh. A well-defined block of subcutaneous fibrosis involving skin and skeletal muscle developed 6 months after irradiation. One experimental group of five pigs was then injected i.m. with 10 mg/10 kg b.wt. of Cu/Zn-SOD, twice a week for 3 weeks, and another experimental group of five was injected with 10 mg/10 kg b.wt. of Mn-SOD, three times a week for 3 weeks. Five irradiated control pigs were injected with physiological serum. Animals were assessed for changes in the density of the palpated fibrotic block and in the dimensions of the projected cutaneous surface. Block depth was determined by ultrasound. Physical and sonographic findings were confirmed by autopsy 12-14 weeks after completing SOD injections. The density, length, width, and depth of the fibrotic block, and the areas and volume of its projected cutaneous surface were compared before treatment, 1, 3, and 6 weeks thereafter, and at autopsy, 12-14 weeks after treatment ended. RESULTS: The experimental animals exhibited no change in behavior and no abnormal clinical or anatomic signs. Whether they were given Cu/Zn- or Mn-SOD, significant and roughly equivalent softening and shrinking of the fibrotic block were noted in all treated animals between the first week after treatment ended and autopsy, when mean regression was 45% for length and width, 30% for depth, and 70% for area and volume. Histologic examination showed completely normal muscle and subcutaneous tissue surrounding the residual scar. This replacement of scar tissue by normal tissue in experimental animals and the 50% decrease in the linear dimensions of the scar were comparable to the results obtained in previous clinical studies and highly significant compared to the clinical and autopsy results for the control animals. CONCLUSIONS: Our results are striking and comparable to the results obtained in our previous clinical study after liposomal Cu/Zn-SOD treatment. To our knowledge, this is the first time that two agents have been shown to reverse the radiation-induced fibrotic process in experimental animals and to permit the regeneration of normal tissue in a zone of well-established postirradiation fibrosis.

Recombinant polypeptides derived from the fibrin binding domain of fibronectin are potential agents for the imaging of blood clots.

Thrombus formation in the circulation is accompanied by covalent linkage of fibronectin (FN) through transglutamination of glutamine no. 3 in the fibrin binding amino terminal domain (FBD) of FN. We have exploited this phenomenon for thrombus detection by the employment of radioactively-labelled recombinant polypeptide molecules derived from the 5-finger FBD of human FN. Three recombinant FBD polypeptides, 12 kDa ("2 fingers"), 18.5 kDa ("3 fingers") and 31 kDa FBD ("5 fingers"), were prepared and compared to native FN-derived 31 kDa-FBD with respect to their ability to attach to fibrin clots in vitro and in vivo. The accessibility of Gln-3 in these molecules was demonstrated by the incorporation of stoichiometric amounts of 14C-putrescine in the presence of plasma transglutaminase. Competitive binding experiments to fibrin have indicated that, although the binding affinities of the FBD molecules are lower than that of FN, substantial covalent linkage was obtained in the presence of transglutaminase, and even in the presence of excess FN or heparin. The biological clearance rates of radioactively labelled FBD molecules in rats and rabbits were much higher than those of FN and fibrinogen, thus indicating their potential advantage for use as a diagnostic imaging tool. Of the three molecules, the 12 kDa FBD exhibited the highest rate of clearance. The potential of the 12 kDa and 31 kDa FBDs as imaging agents was examined in a stainless steel coil-induced thrombus model in rats and in a jugular vein thrombus model in rabbits, using either [125I] or [111In]-labelled materials. At 24 h, clot-to-blood ratios ranged between 10 and 22 for [125I]-12 kDa FBD and 40 and 60 for [111In]-12 kDa FBD. In the rat model, heparin did not inhibit the uptake of FBD. Taken together, the results indicate that recombinant 12 kDa FBD is a good candidate for the diagnosis of venous thrombosis.

On the synergistic action of androgen and FSH on progestin secretion of cultured rat granulosa cells. Cellular and mitochondrial cholesterol metabolism.

The effect of FSH and androgen on the conversion of cholesterol into progesterone by cultured rat granulosa cells (GC) was studied in intact cells or mitochondrial preparations. Culture of GC for immature hypophysectomized diethylstilbestrol-treated rats for 48 h in the presence of ovine FSH (5 microgram/ml) alone, or FSH + testosterone (Te; 0.5 microgram/ml) caused a slight increase in the activity of the mitochondrial marker enzyme succinic dehydrogenase, while Te had no effect. Culture with the hormones for 48 h had no significant effect on the levels of free and esterified cellular cholesterol. GC monolayers after 48 h with or without FSH and Te converted [3H]cholesterol into 4 major metabolites, 3 of which were secreted into the medium and, in thin-layer chromatographic behavior, resembled pregnenolone, progesterone and 20 alpha-dihydroprogesterone. The total amount of the 3 C-21 steroids was higher (p less than 0.01) in FSH- or Te-treated than in control cells, and combined treatment had a synergistic effect. The uptake of labeled cholesterol (4--10%) was significantly higher (p less than 0.01) in cells pretreated with FSH or Te, whereas a combined FSH and Te treatment had an additive effect. Mitochondria isolated from GC monolayers took up cholesterol in a temperature-dependent fashion, but this uptake was not affected by hormonal pretreatment. In the presence of cyanoketone, the mitochondrial fractions activity converted cholesterol into pregnenolone. This activity was enhanced by FSH or Te (p less than 0.01), and further enhancement was observed with FSH + Te; the combined effect appeared to be more than additive (p = 0.05). The results suggest that both FSH and Te enhance the activity of cholesterol side-chain cleavage, but do not affect the transport of cholesterol into the mitochondria. A possible hormonal effect on a pre-mitochondrial step is discussed.

Studies on the synergistic effect of androgen on the stimulation of progestin secretion by FSH in cultured rat granulosa cells: a search for the mechanism of action.

Cultures of granulosa cells from immature hypophysectomized DES-treated rats were unable to maintain progestin production of more than 48 h in medium without hormone supplementation or in the presence of FSH only. Production of progestin (20alpha-dihydroprogesterone, as measured by radioimmunoassay) remained unimpaired in the presence of androstenedione (Ad) and was markedly increased in the presence of both Ad and FSH. The combined treatment with FSH and Ad during the first 48 h of culture brought about persistent changes in the cultured cells, since progestin accumulation did not decline upon subsequent removal of these hormones during days 3 and 4 of culture. Dibutyryl cyclic AMP (DBC) was able to mimic the changes in steroidogenic capability induced by the combined action of FSH and Ad. The extent of [125I]-FSH binding, FSH-stimulable cAMP accumulation and cyclic 3',5'-nucleotide phosphodiesterase activity were not affected by addition of Ad to the culture medium. Ad synergized with DBC in the stimulation of progestin accumulation in granulosa cell cultures. It is suggested that androgen acts at a step in the regulation of progestin biosynthesis distal to cAMP production.

Studies on the synergistic effect of androgen on the stimulation of progestin secretion by FSH in cultured rat granulosa cells: progesterone metabolism and the effect of androgens.

Metabolic transformations of progesterone in cultures of granulosa cells from immature hypophysectomized rats treated with diethylstilbestrol were studied in relation to the synergistic action of exogenous androgen and FSH on progestin (progesterone and 20alpha-dihydroprogesterone) accumulation. Androstenedione (Ad; 10 ng/ml) enhanced the sensitivity of rat granulosa cells to this steroidogenic action of FSH, lowering the threshold of the response from greater than 4 ng/ml (FSH alone) to 0.8 ng/ml in the presence of Ad. A synergistic effect with FSH was also shown by various 5alpha-androstane derivatives. They were, however, less effective than the parent delta4-3 keto androstenes. Progesterone underwent extensive 5alpha-reduction during culture, leading to accumulation of endogenous 5alpha-pregnane compounds, and to transformation of labelled progesterone into 5 alpha-reduced radiometabolites. These compounds corresponded in gas-liquid and thin-layer chromatographic behaviour to 3alpha-hydroxy-5alpha-pregnan-20-one, 20alpha-hydroxy-5alpha-pregnan-3-one and 5alpha-pregnane-3alpha,20alpha-diol. The rate of 5alpha-reduction of progestins was not affected by the presence of exogenous Ad (1 microgram/ml), ruling out the possibility that the effect of androgen on progestin accumulation depends on competitive inhibition of 5alpha-reductase. An involvement of androgen of thecal origin in the enhancement of the sensitivity of the FSH-responsive mechanism in granulosa cells is suggested.

A synergistic effect of androgen on the stimulation of progesterone secretion by FSH in cultured rat granulosa cells.

Granulosa cells from preovulatory follicles (PO) or from the enlarged preantral follicles of hypophysectomized immature diethylstilbestrol-treated (Hx-DES) rats were cultured with various combinations of FSH, androst-4-ene-3,17-dione (Ad), estradiol-17beta and dibutyryl cyclic AMP (dbcAMP). Progestin levels (progesterone and 20alpha-dihydroprogesterone) in the medium after 2 days of culture were assayed by radioimmunoassay. The control levels of the two progestins were lower for Hx-DES than for PO cells. Rat FSH (NIAMD-1-3;0.1 mug/ml) caused a 2-fold rise in progestin accumulation in both PO and Hx-DES cultures, dbcAMP (1 mM) increased progestin accumulation in PO cultures 4-5-fold, and to an even greater extent (10-20 fold) in Hx-DES cultures. Androstenedione (1.0 mug/ml) augmented progestin accumulation (1.5-3-fold), and synergized the steroidogenic action of FSH: in cells from Hx-DES rats, combined treatment with FSH and Ad caused a 5-10-fold increase over the values obtained with FSH alone. Testosterone and 5alpha-dihydrotestosterone, but not estradiol-17beta or estrone, mimicked these effects of Ad, Ad did not synergize the action of dbcAMP on progestin levels in Hx-DES cultures. It is proposed that androgen may play a role in the development of the FSH-responsive mechanism in preantral granulosa cells.

Enhancement of recombinant tissue-type plasminogen activator thrombolysis with a selective factor Xa inhibitor derived from the leech Hirudo medicinalis: comparison with heparin and hirudin in a rabbit thrombosis model.

OBJECTIVE: To compare the efficacy of Yagin, a factor Xa inhibitor derived from the leech Hirudo medicinalis, with those of heparin and hirudin as adjuncts to recombinant tissue-type plasminogen activator (rTPA) thrombolysis in a rabbit thrombosis model. METHODS: Thirty-one animals were allocated randomly to three groups, all administered four boluses of 0.25 mg/kg rTPA every 10 min for 30 min, 17 mg/kg aspirin intravenously, and heparin (as a 100 IU/kg bolus followed by infusion of 50 IU/kg heparin per h), hirudin (as a 2 mg/kg bolus followed by infusion of 1 mg/kg hirudin per h), or Yagin (as an 80 micrograms/kg bolus followed by infusion of 43 micrograms/kg Yagin per h). RESULTS: Administration of Yagin was associated with a significant acceleration of the reflow time, this time being 14.5 +/- 1.2 min with Yagin, 25.8 +/- 5.2 min with heparin (P < 0.0001, versus Yagin), and 28.7 +/- 16.0 min with hirudin (P = 0.012, versus Yagin). Overall patency did not differ significantly among the three groups. CONCLUSIONS: At the indicated single doses, inhibition of factor Xa by a relatively low concentration of Yagin was found to be superior than that with either heparin or hirudin for accelerating rTPA thrombolysis.

Metabolism of lysergic acid diethylamide (LSD) to 2-oxo-3-hydroxy LSD (O-H-LSD) in human liver microsomes and cryopreserved human hepatocytes.

The metabolism of lysergic acid diethylamide (LSD) to 2-oxo-3-hydroxy lysergic acid diethylamide (O-H-LSD) was investigated in liver microsomes and cyropreserved hepatocytes from humans. Previous studies have demonstrated that O-H-LSD is present in human urine at concentrations 16-43 times greater than LSD, the parent compound. Additionally, these studies have determined that O-H-LSD is not generated during the specimen extraction and analytical processes or due to parent compound degradation in aqueous urine samples. However, these studies have not been conclusive in demonstrating that O-H-LSD is uniquely produced during in vivo metabolism. Phase I drug metabolism was investigated by incubating human liver microsomes and cryopreserved human hepatocytes with LSD. The reaction was quenched at various time points, and the aliquots were extracted using liquid partitioning and analyzed by liquid chromatography-mass spectrometry. O-H-LSD was positively identified in all human liver microsomal and human hepatocyte fractions incubated with LSD. In addition, O-H-LSD was not detected in any microsomal or hepatocyte fraction not treated with LSD nor in LSD specimens devoid of microsomes or hepatocytes. This study provides definitive evidence that O-H-LSD is produced as a metabolic product following incubation of human liver microsomes and hepatocytes with LSD.

Identification and quantitation of 11-nor-delta9-tetrahydrocannabivarin-9-carboxylic acid, a major metabolite of delta9-tetrahydrocannabivarin.

After incubation of delta9-tetrahydrocannabivarin with human hepatocytes, a major metabolic product was detected by gas chromatography-mass spectrometry that showed identical retention time and mass spectrum to the synthetic 11-nor-delta9-tetrahydrocannabivarin-9-carboxylic acid (11-nor-delta9-THCV-9-COOH). Analysis of human urine specimens from marijuana users and plasma samples from Marinol users showed that 11-nor-delta9-THCV-9-COOH was only present in urine specimens of marijuana users. These results supported the conclusion that identification of 11-nor-delta9-THCV-9-COOH in a donor's urine specimen indicates the use or ingestion of cannabis-related product(s) and would not explain the sole use of Marinol.

Non-traumatic perforation of the small intestine. Report of 13 cases and review of the literature.

BACKGROUND/AIMS: Non-traumatic perforation of the small intestine (NTPSI) is a rare entity. It is possible that nowadays, the etiology of NTPSI has changed and that mortality might be lower. The aim of this study was to compare a recent series with previous series published in the literature. METHODOLOGY: During 13 years (1984-1996), 13 patients were diagnosed by laparotomy and histology as cases of NTPSI. RESULTS: The various etiologies of the perforations were: Crohn's disease in 6 (46%) patients, an ingested foreign body in 3 (23%) patients, primary intestinal malignancies (B-cell high-grade lymphoma and leiomyosarcoma) in 2, an internal hernia and an unclear etiology ("idiopathic") in 1 patient each. The symptoms were non-specific and an abdominal X-ray showed free-air in only 1 of 11 patients. Only one patient died postoperatively. CONCLUSIONS: NTPSI remains a rare entity with an incidence of 1 case/year/350,000 population. Compared to seven previous series from industrialized countries, it seems that Crohn's disease has recently become the major etiology for NTPSI, probably due to the increasing prevalence of this disease. It is possible that many of the frequent "idiopathic" cases diagnosed in the past were due to non-steroidal anti-inflammatory drugs. While in developing countries, typhoid fever remains a major cause of NTPSI, opportunistic infections are recently reported in industrialized countries. The diagnosis of NTPSI is usually made at laparotomy. In most cases, resection and primary anastomosis is appropriate. Mortality rates might be lower than in the past.

Sodium hyaluronate as a tool in strabismus surgery in rabbits.

BACKGROUND AND OBJECTIVE: The authors tested whether coating tissue with sodium hyaluronate (Na-HA) reduced postoperative adhesions and accelerated the healing process in strabismus surgery. MATERIALS AND METHODS: The surgical technique was tested during recession and resection operations performed on 30 rabbits and was compared with the use of NaCl 0.9%. Clinical, biomicroscopic examinations were performed on postoperative days 1, 2, 7, and 30 and histopathologic examinations were performed on postoperative days 2, 7, and 30. RESULTS: Clinically, there were no statistically significant differences between the study group and the control group. Also, there were no statistically significant differences between the two groups for most of the histopathologic criteria; however, new vessel formation was smaller with Na-HA than without it. Statistical significance was defined as P < .05. CONCLUSION: The authors found no significant positive effect of Na-HA on postoperative healing in rabbits.