Utilization of influenza immunization in adults with Crohn's disease-a longitudinal, population-based study.

BACKGROUND: The incidence of vaccine-preventable disease is increasing. Several guidelines recommend annual influenza vaccination for patients with inflammatory bowel disease. METHODS: Using the Business Objects database of Clalit Health Services in the Tel Aviv district we identified all patients older than 18 years with a diagnosis of Crohn's disease (CD) on December 31, 2005. This cohort was followed until December 31, 2012. Subjects without inflammatory bowel disease older than 50 years served as controls. The uptake of annual influenza vaccination was recorded. RESULTS: The study included 515 patients with CD (267 [51.8%] men, age 48.9 ± 17.5 years, disease duration 142.7 ± 56.9 months) and 2960 controls (1262 [42.6%] men, P < 0.01, age 68.9 ± 11.1 years, P < 0.01). The mean number of influenza vaccines received from 2006 to 2012 was 2.08 ± 2.46 and 3.40 ± 2.71 in CD and controls, respectively (P < 0.01). Uptake was higher in patients with CD aged 50 to 59 years and 60 to 69 years, compared with controls (0.45 ± 0.04 versus 0.24 ± 0.01, P < 0.01 and 0.64 ± 0.06 versus 0.50 ± 0.01, P = 0.04, respectively). Vaccination uptake increased significantly over time in both groups (P < 0.01). Predictors of vaccination in CD included age, female sex, immunosuppression, and cardiovascular disease. CONCLUSIONS: Uptake of influenza vaccination in CD has increased over the past 7 years, and among subjects older than 50 years, uptake remains higher in age-matched controls. Nevertheless, overall uptake remains low, particularly in young males.

THR-18, a 18-mer peptide derived from PAI-1, is neuroprotective and improves thrombolysis by tPA in rat stroke models.

OBJECTIVE: The thrombolytic treatment of stroke is limited by a narrow therapeutic time window and is associated with significant adverse side effects. To improve this situation, the modulation of tissue-type plasminogen activator (tPA) activity by a synthetic plasminogen activator inhibitor-1-derived 18-mer peptide (THR-18) was examined in two models of stroke in rats. METHODS: In the first model (thromboembolic), stroke was induced by intra-carotid injection of micro-clots to rats, and tPA (6 mg/kg) was intravenously infused for 30 minutes with or without THR-18 (1 mg/kg) at 4 hours post-induction. In the second model [transient middle cerebral artery occlusion (tMCAO)], stroke was induced for 2 hours by a transient mechanical occlusion. tPA and/or THR-18 (0.02, 0.1, and 1 mg/kg) were intravenously infused for 60 minutes at the time of reperfusion. RESULTS: In the thromboembolic model, cerebral blood flow, measured before and up to 5.5 hours post-induction, revealed that tPA administration caused reperfusion of flow at 30 minutes post-infusion. Later on, an additional increase in reperfusion was seen in the tPA+THR-18 group, and not with tPA alone. In both models, the frequency of intracranial hemorrhage in the tPA-treated group was found to be significantly higher than the control, and this tPA effect was attenuated by THR-18. In the thromboembolic study, infarct size and brain edema were similar in the control and tPA-treated rats. However, the combination of tPA and THR-18 caused a statistically significant reduction in both parameters (infarct size 17.8 versus 25.0%, brain edema 5 versus 8%, tPA+THR-18 versus control, respectively). In the tMCAO mechanical model, infarct size and brain edema were both increased by tPA treatment as compared to the control group, and this increase was markedly diminished by THR-18 co-administration. Neurobehavioral assessment of the tMCAO animals performed at 72 hours post-stroke induction revealed significant improvements (P<0.05-0.01) in neuroscores in all groups of animals treated with peptide-tPA, as compared to the tPA monotherapy group. A significant (P<0.05) improvement in the neurological outcome was also seen in the THR-18 monoterapy group, as compared to the control animals, thus demonstrating a clear neuroprotective effect by the peptide on its own. DISCUSSION: The results support the use of THR-18 together with tPA in the thrombolytic therapy of stroke, in order to achieve better patency, less tPA-induced damage, and possibly a widening of tPA therapeutic time window.

[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.

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.

Gastric plasmacytoma and Helicobacter pylori infection.

A 59-year-old man with a history of melena and upper abdominal pain was referred to our hospital. An upper endoscopy was performed, and a gastric ulcer was found bordering the antrum and stomach body. Multiple biopsies from the lesion showed monoclonal plasmacytic infiltration of the mucosa, consistent with the diagnosis of plasmacytoma. Helicobacter pylori was also identified. Triple therapy failed and quadruple therapy eradicated the H. pylori, confirmed by repeated biopsies. Healing of the gastric lesion followed the treatment. Multiple biopsies from the scar and the entire stomach showed complete regression of the plasmacytoma. The association between gastric plasmacytoma and H. pylori is discussed.

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.

Phenolic compounds from Miconia myriantha inhibiting Candida aspartic proteases.

Assay-guided fractionation of the ethanol extract of the twigs and leaves of Miconia myriantha yielded two new compounds, mattucinol-7-O-[4' ',6' '-O-(S)-hexahydroxydiphenoyl]-beta-D-glucopyranoside (1) and mattucinol-7-O-[4' ',6' '-di-O-galloyl]-beta-D-glucopyranoside (2), along with mattucinol-7-O-beta-D-glucopyranoside (3), ellagic acid (4), 3,3'-di-O-methyl ellagic acid-4-O-beta-D-xylopyranoside, and gallic acid. Complete (1)H and (13)C NMR assignments of compound 1, which possesses a hexahydroxydiphenoyl unit, were achieved using the HMBC technique optimized for small couplings to enhance the four-bond and two-bond H/C correlations. Compounds 1 and 4 showed inhibitory effects against Candida albicans secreted aspartic proteases, with IC(50) of 8.4 and 10.5 microM, respectively.

A new naphthopyrone derivative from Cassia quinquangulata and structural revision of quinquangulin and its glycosides.

A novel naphthopyrone derivative, named quinquangulone (1), has been isolated from Cassia quinquangulata, along with the known compounds quinquangulin (2) and its two glycosides (3 and 4), rubrofusarin (5) and its two glycosides (6 and 7), nor-rubrofusarin (8) and its 6-O-glucoside (9), and three stilbenes (10-12). The structure of quinquangulone was established by spectral interpretation as 5,9-dihydroxy-8-methoxy-2,9-dimethyl-6-oxo-4H,6H,9H-naphtho-[2,3-b]pyran-4-one. Reinvestigation of the NMR spectra of quinquangulin led to revision of its structure as 5,6-dihydroxy-8-methoxy-2,9-dimethyl-4H-naphtho[2,3-b]pyran-4-one (2a). The structures of two quinguangulin glycosides, 3 and 4, were also revised accordingly. Compound 2a exhibited activity against Staphylococcus aureus and methicillin-resistant S. aureus (MIC, 3.125 and 6.25 microg/mL, respectively).

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.

Enantioselective synthesis and complement inhibitory assay of A/B-ring partial analogues of oleanolic acid.

A series of oleanolic acid A/B-ring partial analogues was synthesized and tested for their complement inhibitory activity as well as cytotoxic properties. All target compounds and one intermediate exhibited moderate complement inhibitory potency. These compounds also showed cytotoxicity on malignant melanoma cell line, SK-MEL.

Dihydrochalcones from Piper longicaudatum.

Bioactivity-guided fractionation of an ethanolic extract of the leaves and twigs of Piper longicaudatum Trelease & Yunker (Piperaceae) resulted in the isolation of one new (1) and three known (2-4) dihydrochalcones. The known compounds are: 2',6'-dihydroxy-4'-methoxydihydrochalcone (2), 2',6',4-trihydroxy-4'-methoxydihydrochalcone (asebogenin) (3), and 2'-hydroxy-4'-methoxy-2'-[1-hydroxy-1-methylethyl]-2",3"-dihy- drofurano[4",5":5',6"]-3"-[2-hydroxy-5-methoxycarbonylphe- nyl]dihydrochalcone (piperaduncin B) (4). The new compound is 2'-hydroxy-4'-methoxy-2"-[2-hydroxy-5-methoxycarbonyl- phenyl]-furano[4",5":5',6']-dihydrochalcone (longicaudatin) (1). Compounds 1-4 were tested for antibacterial activity against S. aureus and methicillin-resistant S. aureus (MRSA); only compound 3 showed inhibitory activity (IC50 of 10 and 4.5 micrograms/ml, respectively).

Antifungal chalcones from Maclura tinctoria.

Five prenylated flavonoids, including one new natural product, were isolated from an ethanol extract of the leaves of Maclura tinctoria (L.) Gaud. The new compound has been characterized as 2',4',4,2''-tetrahydroxy-3'-[3''-methylbut-3''-enyl]chalcone (1). The known compounds were identified as 2',4',4-trihydroxy-3'-[3''-methylbut-3''-enyl]chalcone (isobavachalcone) (2), 4,2'-dihydroxy-2''-[1-hydroxy-1-methylethyl]-2'',3''-dihydrofurano[4'',5'':3',4']chalcone (bakuchalcone) (3), 4,4',5''-trihydroxy-6'',6''-dimethyldihydropyrano[2'',3'':5',6'']chalcone (bavachromanol) (4), and 5,7,3',4'-tetrahydroxy-6,8-diprenylisoflavone (6,8-diprenylorobol) (5). All the isolated compounds were evaluated against the AIDS-related opportunistic fungal pathogens, Candida albicans and Cryptococcus neoformans. Compound 2 was active against both yeasts.

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.

New antimycobacterial saponin from Colubrina retusa.

A new jujubogenin saponin was isolated from the stems of Colubrina retusa and identified as jujubogenin 3-O-alpha-L-arabinofuranosyl (1-->2)-[3-O-(trans)-p-coumaroyl-beta-D-glucopyranosyl (1-->3)]-alpha-L-arabinopyranoside (4) on the basis of chemical and spectroscopic data. The antimycobacterial activity expressed as minimum inhibitory concentration (MIC) for compound 4 was 10 microg/mL.

Synthesis and evaluation of potential complement inhibitory semisynthetic analogs of oleanolic acid.

A number of semisynthetic analogs of oleanolic acid have been synthesized and tested for their complement inhibitory, cytotoxic and apoptotic activities. Among these, compounds 10 and 17 exhibited complement inhibitory potency superior to oleanolic acid. Both have also shown a moderate improvement in in vitro therapeutic index (T.I.).

Evaluation of triage decisions for intensive care admission.

OBJECTIVE: To assess physician decision-making in triage for intensive care and how judgments impact on patient survival. DESIGN: Prospective, descriptive study. SETTING: General intensive care unit, university medical center. INTERVENTIONS: All patients triaged for admission to a general intensive care unit were studied. Information was collected for the patient's age, diagnoses, surgical status, admission purpose, Acute Physiology and Chronic Health Evaluation (APACHE) II score, and mortality. The number of available beds at the time of triage and reasons for refused admission were obtained. MEASUREMENTS AND MAIN RESULTS: Of 382 patients, 290 were admitted, 92 (24%) were refused admission, and 31 were admitted at a later time. Differences between admission diagnoses were found between patients admitted or not admitted (p < .001). Patients refused admission had higher APACHE II scores (15.6+/-1.5 admitted later and 15.8+/-1.4 never admitted) than did admitted patients (12.1+/-.4; p < .001). The frequency of admitting patients decreased when the intensive care unit was full (p < .001). Multivariate analysis revealed that triage to intensive care correlated with age, a full unit, surgical status, and diagnoses. Hospital mortality was lower in admitted (14%) than in refused patients (36% admitted later and 46% never admitted; p < .01) and in admitted patients with APACHE II scores of 11 to 20 (p = .02). The 28-day survival of patients was greater for admitted patients compared with patients never admitted (p = .01). CONCLUSIONS: Physicians triage patients to intensive care based on the number of beds available, the admission diagnosis, severity of disease, age, and operative status. Admitting patients to intensive care is associated with a lower mortality rate, especially in patients with APACHE scores of 11 to 20.

Antifungal jujubogenin saponins from Colubrina retusa.

Antifungal assay-guided isolation of the 95% ethanol extract of the stems of Colubrina retusa yielded jujubogenin 3-O-alpha-L-arabinofuranosyl(1-->2)-[beta-D-glucopyranosyl (1-->3)]-alpha-L-arabinopyranoside (1), which showed modest growth-inhibitory effects against Candida albicans, Cryptococcus neoformans, and Aspergillus fumigatus (MICs, 50 microg/mL). In addition, two new minor saponins, jujubogenin 3-O-alpha-L-arabinofuranosyl(1-->2)-[2-O-(trans, cis)p-coumaroyl-beta-D-glucopyranosyl(1-->3)]-alpha-L-arabinopy ranosi de (2), and jujubogenin 3-O-(5-O-malonyl)-alpha-L-arabinofuranosyl (1-->2)-[beta-D-glucopyranosyl(1-->3)]-alpha-L-arabinopyranoside (3), were obtained. Saponin 2 was marginally active against only C. neoformans, with a MIC of 50 microg/mL, while 3 was inactive. NMR spectroscopy was used extensively for the structure determination of these compounds. The previously reported ambiguity of the NMR assignments of jujubogenin saponins for carbons -26 to -29 was clarified by a comprehensive analysis of the NMR spectra of 1.