Evaluation of five commercial serological tests for the detection of Helicobacter pylori infection in Chinese

BACKGROUND: Commercial serological tests for the detection of Helicobacter pylori infection must be locally validated. We evaluated the accuracy of five commercial tests in the Chinese population. METHODS: Serum samples were collected from patients referred for upper endoscopy. Antral biopsies were taken for histological examination and culture of H. pylori. The gold standard for diagnosing H. pylori infection was positive histological staining and/or positive H. pylori culture. The serum samples were tested for H. pylori antibodies using the following tests: (i) Cobas Core Anti-H. pylori EIA; (ii) GAP IgG; (iii) GAP IgM; (iv) H. pylori microwell EIA (Quidel); and (v) Premier H. pylori. The sensitivity, specificity and accuracy of each test was calculated according to the manufacturers' instructions or according to a new cut-off value. RESULTS: A total of 158 patients were recruited amongst whom 114 (72%) were H. pylori-positive. Indeterminate results varied from 7% to 19%. The accuracy of the tests varied from 57% to 85%. By using new cut-off values, the accuracy was much improved, ranging from 73.4% to 86.7%. CONCLUSIONS: By defining new cut-off values for the Chinese population, we were able to improve the performance of some of the serology tests. This illustrates the importance of local validation.     

Assessment of biodegradability of polymeric microspheresin vivo: Poly (DL-lactic acid), poly (L-lactic acid) and poly (DL-lactide-co-glycolide) microspheres

To confirm a new evaluation technique for biodegradability of biopolymer microspheres in vivo condition, magnetic microsphere system was adopted for tracing the microspheres injected and lodged in mice. Microspheres of poly(DL-lactic acid), poly(L-lactic acid) and poly (DL-lactide-coglycolide)(PLGA) were prepared by solvent-extraction method and their organ distribution and biodegradation in mice was examined. Magnetic microspheres lodged in mice organs were recollected from the homogenates of mice organs with a constant flow magnetic separation apparatus. Recollected microspheres were observed by scanning electron microscopy and also were assayed for their magnetite content by atomic absorption spectrophotometry to evaluate the biodegradability of polymeric microspheres. This method seems to be practical and simple to estimate the biodegradability of biopolymers over the conventional methods.     

Four years' experience with a clinical intervention program: cost avoidance and impact of a clinical coordinator

Four years of data are reported on the drug cost avoidance and the net cost savings associated with a clinical pharmacy intervention program. In 1986 the pharmacy department at a 324-bed nonprofit community medical center began a clinical intervention program by adding one full-time equivalent for providing clinical services. A new clinical pharmacist position was created in 1988. A reorganization in 1989 resulted in further increases in staffing, including the creation of a clinical coordinator position to oversee the intervention program, and in administrative time. Staff pharmacists self-report a broad range of interventions on a clinical documentation form. During the period 1986-1989, monthly data on the number of types of interventions recommended, the percentage of recommendations accepted by the medical staff, and drug cost avoidance were tabulated. Cost avoidance was calculated by subtracting the cost of therapy ordered by the physician from the cost of therapy initiated as a result of the intervention. Net drug cost savings were calculated by subtracting from cost avoidance the cost of pharmacist time required for performing the interventions. The average number of interventions per month ranged from 170 in 1986 to 292 in 1990. During an 18-month period before the clinical coordinator was added, average monthly cost avoidance and net savings were $4932 and $3739, respectively. Average monthly cost avoidance increased to $6244 and savings to $4644 in a 12-month period after the clinical coordinator was added. A four-year study of a clinical intervention program showed that the dollar value and impact outlasted the initial success expected for such programs.     

Synthesis and in vitro LTD4 antagonist activity of bicyclic and monocyclic cyclopentylurethane and cyclopentylacetamide N-arylsulfonyl amides

The dissociation constants (KB) at the LTD4 receptor on guinea pig trachea of a series of monocyclic and bicyclic cyclopentylurethane and cyclopentylacetamide N-arylsulfonyl amides have been measured. The KB was found to be remarkably tolerant of changes in the electronic constitution and lipophilicity of the bicyclic ring system (template). Thus, N-[4[[6-[[(cyclopentyloxy)carbonyl]amino]benzimidazol-1- yl]methyl]-3-methoxybenzoyl]benzenesulfonamide (11a) and N-[4-[[5-[[(cyclopentyloxy)carbonyl]amino]benzo[b]thien-3- yl]methyl]-3-methoxybenzoyl]benzene-sulfonamide (25a) had closely similar affinities (pKB, 9.20 and 9.31, respectively; LTE4 as agonist). It has been shown that the hetero-ring of the template need not be aromatic in order to achieve high affinity, since indoline 31 and 2,3-dihydrobenz-1,4-oxazines 37a-c had pKBs greater than 9. Further, it has been shown that an o-aminophenone (see 42 and Figure 3) can function as a template; the template in 42 [see iii] is bicyclic by virtue of the presence of an intramolecular hydrogen bond. In contrast, when the template is a phenyl ring (48), receptor affinity is markedly reduced. These findings support the notion that central bicyclic ring system in this family of peptidoleukotriene antagonists is a molecular feature which helps to preorganize the acylamino and acidic chains and thereby facilitate the molecular recognition event.     

The amphetamine sensitization model of schizophrenia: relevance beyond psychotic symptoms?

Rationale

A sensitized dopamine system may be linked to the genesis of psychotic symptoms in schizophrenia. Following withdrawal from amphetamine exposures, psychotic-like traits have been robustly demonstrated, but the presence of cognitive/mnemonic deficits remains uncertain.

Methods

Adult male Lewis and Fischer rats, differing in cognitive performance, were exposed intermittently to escalating doses of amphetamine over 5 weeks. This was effective in producing behavioral sensitization to a subsequent amphetamine challenge. Following 27 days of drug withdrawal, the animals were assessed in Pavlovian conditioning, object recognition, and spatial working memory. In addition, prepulse inhibition (PPI), spontaneous motor activity, and anxiety-like behavior were measured.

Results

Amphetamine pretreatment induced behavioral sensitization in both rat strains similarly. Working memory was enhanced in Fischer but not Lewis rats following withdrawal. Spontaneous novel object preference was enhanced in sensitized Fischer rats, but was impaired in sensitized Lewis rats, thus effectively reversing the strain difference in non-sensitized controls. In contrast, Pavlovian fear conditioning remained unaffected and so were anxiety-like behavior, open field activity, and PPI.

Conclusion

The face validity of the amphetamine withdrawal model for cognitive deficits was limited to the object recognition memory impairment observed in sensitized Lewis rats. Yet, the possibility that enhancing dopaminergic neurotransmission may facilitate object recognition and spatial working memory performance was demonstrated in sensitized Fischer rats. Identification of the mechanisms underlying such strain-dependent effects would be instrumental in the further specifications of the construct validity, and therefore the limitations and potential of the amphetamine sensitization model of schizophrenia.     

2003 survey of Canadian radiation oncology residents

PURPOSE: Radiation oncology's popularity as a career in Canada has surged in the past 5 years. Consequently, resident numbers in Canadian radiation oncology residencies are at all-time highs. This study aimed to survey Canadian radiation oncology residents about their opinions of their specialty and training experiences. METHODS AND MATERIALS: Residents of Canadian radiation oncology residencies that enroll trainees through the Canadian Resident Matching Service were identified from a national database. Residents were mailed an anonymous survey. RESULTS: Eight of 101 (7.9%) potential respondents were foreign funded. Fifty-two of 101 (51.5%) residents responded. A strong record of graduating its residents was the most important factor residents considered when choosing programs. Satisfaction with their program was expressed by 92.3% of respondents, and 94.3% expressed satisfaction with their specialty. Respondents planning to practice in Canada totaled 80.8%, and 76.9% plan to have academic careers. Respondents identified job availability and receiving adequate teaching from preceptors during residency as their most important concerns. CONCLUSIONS: Though most respondents are satisfied with their programs and specialty, job availability and adequate teaching are concerns. In the future, limited time and resources and the continued popularity of radiation oncology as a career will magnify the challenge of training competent radiation oncologists in Canada.     

Oxaliplatin, a potent inhibitor of survivin, enhances paclitaxel-induced apoptosis and mitotic catastrophe in colon cancer cells

BACKGROUND: Clinical studies have demonstrated that oxaliplatin, a novel platinum derivative, is a potent chemotherapeutic agent, especially when combined with other reagents. The aim of the present study was to explore the mechanism of such action. METHODS: Using colon cancer cell lines, we examined changes in cell cycle, apoptosis and mitotic catastrophe induced by oxaliplatin and/or paclitaxel. RESULTS: Oxaliplatin at its IC(50) induced apoptosis and cell cycle arrest at G(2)-M phase. Western blot analyses indicated that oxaliplatin decreased mitosis-commencing protein cdc2 and anti-apoptotic proteins, phospho-Bcl(2) and Bcl-xl in the three colon cancer cells tested. Since cdc2 stabilizes survivin, a putative IAP (inhibitor of apoptosis) family member, through phosphorylation of Thr34, we examined the level of survivin and found a marked decrease due to oxaliplatin. This finding is of particular interest because survivin is a promising molecular target against various human cancers and a key molecule involved in both apoptosis and mitotic catastrophe. When used in combination with paclitaxel (taxol), a putative apoptosis-inducing reagent, the isobologram indicated that the taxol-oxaliplatin sequence or taxol plus oxaliplatin had synergic or additive effects, while the oxaliplatin-taxol sequence resulted in a prominent antagonism. The taxol-oxaliplatin sequence caused marked growth inhibition of DLD1 and SW480 cells, possibly due to upregulation of apoptotic and non-apoptotic pathways, respectively. Morphological surveys indicated that the non-apoptotic process could be mitotic catastrophe. CONCLUSION: Our results suggest that oxaliplatin that potently inhibited survivin may exert outstanding cytotoxic effects when combined with certain chemoreagents through enhancement of apoptosis and mitotic catastrophe.     

Safety and efficacy of weight training in recent breast cancer survivors to alter body composition, insulin, and insulin-like growth factor axis proteins.

BACKGROUND: This randomized controlled trial assessed the safety and effects of twice-weekly weight training among recent breast cancer survivors. Outcomes included body size and biomarkers hypothesized to link exercise and breast cancer risk. METHODS: A convenience sample of 85 recent survivors was randomized into immediate and delayed treatment groups. The immediate group trained from months 0 to 12; the delayed treatment group served as a no exercise parallel comparison group from months 0 to 6 and trained from months 7 to 12. Measures at baseline, 6 and 12 months included body weight, height, body fat, lean mass, body fat %, and waist circumference, as well as fasting glucose, insulin, insulin resistance, insulin-like growth factor-I (IGF-I), IGF-II, and IGF-binding protein-1, IGFBP-2, and IGFBP-3. Injury reporting was standardized. RESULTS: The intervention resulted in significant increases in lean mass (0.88 versus 0.02 kg, P < 0.01), as well as significant decreases in body fat % (-1.15% versus 0.23%, P = 0.03) and IGF-II (-6.23 versus 28.28 ng/mL, P = 0.02) comparing immediate with delayed treatment from baseline to 6 months. Within-person changes experienced by delayed treatment group participants during training versus no training were similar. Only one participant experienced a study related injury that prevented continued participation. CONCLUSION: Twice-weekly weight training is a safe exercise program for recent breast cancer survivors that may result in increased muscle mass, as well as decreased body fat % and IGF-II. The implications of these results on cancer recurrence or survival may become more evident with longer exercise intervention trials among breast cancer survivors.     

Igf system components as prognostic markers in breast cancer

The insulin-like growth factor (IGF) family of ligands, receptors, and binding proteins can regulate breast cancer cell proliferation in vitro, and interruption of these pathways inhibits IGF-mediated cell proliferation. If the IGF family members are key regulators of breast cancer growth and progression in vivo, we would expect their expression to be an indicator of the prognosis of the disease. Thus, measurement of IGF expression may provide an indicator of the growth effect within a tumor, and provide new targets for treatment of the disease. In this review we will summarize the data generated thus far indicating that IGF family members are indicators of prognosis of breast cancer, and that measurement of the whole IGF family in concert may provide useful information for treatment strategies of breast cancer.     

Rabeprazole-based 3-day and 7-day triple therapy vs. omeprazole-based 7-day triple therapy for the treatment of Helicobacter pylori infection

BACKGROUND: Rabeprazole is a new proton pump inhibitor with more potent acid suppressive and anti-Helicobacter effects. AIM: To compare two different regimens of rabeprazole-based triple therapy vs. 7-day omeprazole-based triple therapy for the eradication of Helicobacter pylori infection. METHOD: Patients with proven H. pylori infection were randomized to receive: (i) 7-day rabeprazole, 10 mg, amoxicillin, 1000 mg, and clarithromycin, 500 mg, all twice daily; (ii) 3-day rabeprazole, 20 mg, amoxicillin, 1000 mg, and clarithromycin, 500 mg, all twice daily; or (iii) 7-day omeprazole, 20 mg, amoxicillin, 1000 mg, and clarithromycin, 500 mg, all twice daily. Endoscopy (CLO test, histology) was performed before randomization and 6 weeks after drug treatment. RESULTS: One hundred and seventy-three patients were randomized. H. pylori eradication rates (intention-to-treat, n=173/per protocol, n=167) were 88%/91% for 7-day rabeprazole-based therapy, 72%/72% for 3-day rabeprazole-based therapy and 82%/89% for 7-day omeprazole-based therapy, respectively. The per protocol eradication rate was significantly better in the 7-day rabeprazole-based therapy and 7-day omeprazole-based therapy groups when compared to the 3-day rabeprazole-based therapy group (P=0.01 and P=0.04, respectively). Compliance was excellent and all three regimens were well tolerated. CONCLUSIONS: The efficacy of seven-day rabeprazole-based triple therapy is similar to 7-day omeprazole-based triple therapy for the eradication of H. pylori infection.