Blockade of diabetic vascular injury by controlling of AGE-RAGE system

Vascular complications result in disabilities and short life expectancy in diabetic patients. During prolonged hyperglycemic exposure, non-enzymatically glycated protein derivatives termed advanced glycation endproducts (AGE) are formed at an accelerated rate and accumulated in blood and in tissues. Studies performed in vitro and in vivo revealed AGE and their receptor RAGE as the major accounts for vascular cell derangement characteristic of diabetes. The AGE-RAGE system would thus be considered as a candidate molecular target for overcoming diabetic vascular complications. Potential preventive and therapeutic approaches toward it include inhibition of AGE formation, breakage of preformed AGE-proteins crosslinks, blockade of AGE-RAGE interactions with RAGE competitors or antagonists and RAGE-specific signaling inhibition.     

Home blood-pressure monitoring among hypertensive patients in an Asian population

Hypertension is a principal cause of mortality and morbidity in Singapore. The use of home blood-pressure monitoring (HBPM) to assess hypertensive control with digital devices in the local multi-racial population is unknown. The study determined the factors associated with hypertensive patients' use of HBPM in primary care in a multi-racial Asian population. Randomized cross-sectional questionnaire survey of hypertensive patients managed in a district polyclinic. A model predicting use of HBPM was constructed by univariate and multivariate logistic regression. A total of 224 eligible subjects were randomly selected from 1943 patients. Response rate was 78.1% (n = 175). In all, 61.7% of them were aware of HBPM but only 24% used HBPM. Using multivariate analysis by stepwise backward regression, the final fitted model showed that HBPM was associated with higher patients' socioeconomic status: (adjusted OR for middle-income status = 2.85, 95% CI: 1.2-6.78, P = 0.018; adjusted OR for high-income status = 3.46, 95% CI: 1.22-9.87, P = 0.020) and their documented diastolic BP (adjusted OR for diastolic BP > 80 mmHg = 2.26, 95% CI: 1.06-4.82, P = 0.034). Nonusers cited failure to recognize benefits (54.1%), lack of HBPM awareness (29.3%), understanding of device operation (18.8%) and perception of inaccuracy (10.5%) as deterrents. 76.2% of users were satisfied with HBPM but lacked knowledge in maintenance of devices. In conclusion, 61.7% of the study population were aware of HBPM but only 24% used it. Patients' failure to recognize benefits, lack of awareness, cost and perception of inaccuracy were barriers. Higher socioeconomic status and patient's documented diastolic BP correlated with HBPM usage.     

Antitumor activity of beta-cyclodextrin polymer-camptothecin conjugates

Antitumor activity of linear, beta-cyclodextrin polymer (CDP)-camptothecin (CPT) conjugates (HGGG6, LGGG10, HG6, and HGGG10) is investigated in nude mice bearing human LS174T colon carcinoma tumors. These conjugates differ in polymer molecular mass [97 kDa (H) or 35 kDa (L)], CDP-CPT linker structure [glycine (G) or triglycine (GGG)], and CPT loading [ca. 6 wt % (6) or 10 wt % (10)]. Maximum tolerable doses (MTDs) of the three conjugates, LGGG10, HG6, and HGGG10, are determined to be 36, 9, and 9 mg of CPT/kg, respectively, while the MTD of the CDP alone exceeds 240 mg/kg (highest value investigated). The three CDP-CPT conjugates with high polymer molecular masses (HGGG6, HG6, and HGGG10) demonstrate antitumor activity at their MTDs superior to that of CPT at the same amount and to that of irinotecan at its optimal dose. They also show tumor growth inhibition that is superior to that of the conjugate containing the low-molecular mass polymer (LGGG10) at the same dose of CPT. No significant effects of CPT weight loading or linker structure on tumor growth delay are observed. However, conjugates containing G appear to be less toxic than these with GGG. These antitumor studies demonstrate that the CDP-based conjugates of CPT exhibit tumor growth inhibition superior to that of CPT or irinotecan at the conditions employed in this study. The striking observation is that a short course of treatment with the polymer conjugates gives long-term control of tumor growth that does not occur with either CPT or irinotecan. Intracellular CDPs are demonstrated by analyzing cells that were cultured in the presence of rhodamine-labeled CDP (HRhod) containing medium using both confocal microscopy and flow cytometry. The long-term therapeutic efficacy of CDP-CPT conjugates observed in mice may in part be due to the sustained release of CPT from these conjugates in the acidic, intracellular compartments since these conjugates are shown to have significantly slower release rates at acidic pH than at physiological pH.     

Diagnosis and misdiagnosis of hemifacial spasm: a clinical and video study.

Early recognition of hemifacial spasm (HFS) is important as it can be effectively treated. 203 family physicians participated in a video "test" on HFS. Only 9.4% (19/203) were able to diagnose HFS. 94 (46.3%) of them did not know how to manage the condition. Twenty-two (10.8%) would use steroids as a treatment and 13 (6.4%) felt no treatment was needed. Only 27 (13.3%) indicated that botulinum toxin could be employed to treat HFS. The year of graduation of the doctors significantly correlated with a correct diagnosis (P<0.05). The low positive diagnostic rate (25.7%) of HFS from referrals to the movement disorder clinic corroborated findings from the video test.     

TIA-1+ cytotoxic large T-cell lymphoma of the mediastinum: case report

A 52-year-old previously healthy Caucasian woman presented with superior vena cava syndrome, secondary to compression of a bulky anterior mediastinal mass involving the right lung. Fine-needle aspiration biopsy of the mediastinum yielded large epithelioid cells intermingled with small mature lymphocytes. The epithelioid cells are LCA positive, expressing cytoplasmic CD3 diffusely and TIA-1 focally, but negative for EMA, CD4, CD8, CD15, CD20, CD30, and CD56. The TIA-1+ cytoplasmic granules correlated to the azurophilic granules in Diff-Quik-stained cells, pink granules in Ultrafast Papanicolaou-stained cells, and dense core granules in electron microscopy. In situ hybridization for Epstein-Barr viral RNA was negative. The background small lymphocytes were composed of a majority of CD4+ T-lymphocytes and minority of CD8+ T-lymphocytes. The patient responded well to six cycles of CHOP chemotherapy, followed by radiation with a total dose of 4140 cGy delivered to the mediastinum in 23 fractions. On the chest X-ray taken 6 mo later, there was minimal apical fibrosis with no evidence of an acute intrathoracic pathology. To the best of our knowledge, this case may be the first report of cytotoxic large T-cell lymphoma of the mediastinum.     

The assessment of fatigue in primary Sjögren's syndrome

OBJECTIVE: Disabling fatigue is a prominent feature of primary Sj?gren's syndrome (PSS). We evaluated a number of questionnaires for their ability to discriminate fatigue in PSS from that in other rheumatic disorders and healthy controls. METHODS: 33 female caucasian patients with PSS, 45 with rheumatoid arthritis (RA), 16 with systemic lupus erythematosus (SLE) and 30 controls completed self-administered questionnaires including; Visual Analogue Scales (VAS), the Chalder Fatigue Scale (CFS), the Nottingham Health Profile (NHP) and the Medical Outcomes Short Form 36 Questionnaire (SF-36). RESULTS: All patient groups scored significantly worse than controls on the 'Energy' dimension of the NHP, the fatigue VAS and the 'Vitality' domain of the SF-36. No significant differences were observed between PSS patients and controls using the CFS. CONCLUSIONS: The NHP. VAS and SF-36 are useful in identifying fatigue in these rheumatic disorders. Further work is required to identify the characteristic features of fatigue in these conditions.