The role of acid in the pathogenesis of indomethacin-induced gastric antral ulcers in the rat.

BACKGROUND: The role of acid in the pathogenesis of indomethacin- induced ulcers of the rat gastric antrum was studied by comparing the effects of pretreating animals with both long-acting (loxtidine, AH22216) and short-acting (ranitidine and cimetidine) inhibitors of acid secretion. RESULTS: Ranitidine and cimetidine were much weaker at inhibiting antral damage when compared to their reported potencies as antisecretory agents. In marked contrast, loxtidine and AH22216 inhibited indomethacin-induced antral ulcers at doses similar to their reported potencies as inhibitors of acid secretion. Histological analysis at doses causing near maximal inhibition of macroscopic damage revealed an almost complete absence of ulcers but a large and significant increase in mucosal damage due to superficial erosions. Hourly dosing with hydrochloric acid reversed the protective effect of ranitidine, cimetidine and loxtidine on macroscopic damage and, histologically, this was associated with the widespread appearance of antral ulcers and a reduction in the proportion of mucosal damage caused by superficial erosions. CONCLUSIONS: The results of this study suggest that the pathogenesis of nonsteroidal anti-inflammatory drug (NSAID)-induced antral ulcers involves at least two stages: (1) an initial acid-independent formation of mucosal erosions followed by (2) an acid-dependent conversion of erosions to frank ulcers. Clinically, drugs that suppress acid completely for long periods may be very effective in preventing NSAID-induced gastric antral ulcers.     

Determinants of disabling foot pain in retirement village residents

The aim of this study was to evaluate the relative contribution of structural foot characteristics and comorbidities to the presence of disabling foot pain in older people. One hundred seventy-two people (55 men and 117 women) aged 62 to 96 years (mean +/- SD, 80.1 +/- 6.4 years) who lived in a retirement village underwent tests of foot posture, range of motion, and deformity in addition to completing a medical history questionnaire. Disabling foot pain was determined using the Manchester Foot Pain and Disability Index. Thirty-eight subjects (22%) reported disabling foot pain. Subjects with disabling foot pain had a higher body mass index and were more likely to be female; to report osteoarthritis in the spine, hips, hands or wrists, and feet; and to report pain in the back, hips, and hands or wrists. The only significant difference between the groups regarding structural foot characteristics was that those with disabling foot pain exhibited more severe hallux valgus deformity. The strongest determinants of disabling foot pain revealed by a discriminant function analysis were foot osteoarthritis, pain in the hips, and pain in the hands or wrists. These findings indicate that disabling foot pain in older people is more closely related to pain and osteoarthritis in other body regions than to structural characteristics of the foot, and they suggest that more severe forms of foot pain in older people may be a component of a general chronic pain syndrome or a polyarticular form of osteoarthritis.     

Bringing end-of-life care out of the shadows

Understand what resources are available to help you incorporate palliative and end-of-life care into your nursing practice.     

Effects of experimentally induced plantar insensitivity on forces and pressures under the foot during normal walking

Pressures under the foot during level walking were measured in 15 healthy young adults (8 females, 7 males, mean age 25.7, S.D. 5.3) before and after immersing the feet in ice-cold water (2 °C) for 30 min to evaluate the role of plantar insensitivity on gait patterns. Following ice water immersion, there was a significant decrease in walking speed. Maximum forces and peak pressures under the foot decreased, with the exception of an increase in loading under the third to fifth metatarsal heads. Contact times increased under all regions of the foot, and force–time and pressure–time integrals increased under the second and third to fifth metatarsal head regions. It is concluded that plantar insensitivity significantly alters the distribution, duration, and to a lesser extent, the magnitude of forces and pressures under the foot when walking. These results suggest that in the neuropathic foot, gait changes caused by plantar insensitivity may be partly responsible for the redistribution and altered duration of loading, whereas the increase in the magnitude of forces and pressures are primarily due to other disease-related factors.     

Magnetic resonance imaging of the breast prior to biopsy

Context  Breast magnetic resonance imaging (MRI) has been shown to have high sensitivity for cancer detection and is increasingly used following mammography to evaluate suspicious breast lesions. Objective  To determine the accuracy of breast MRI in conjunction with mammography for the detection of breast cancer in patients with suspicious mammographic or clinical findings. Design, Setting, and Patients  Prospective multicenter investigation of the International Breast MR Consortium conducted at 14 university hospitals in North America and Europe from June 2, 1998, through October 31, 2001, of 821 patients referred for breast biopsy for American College of Radiology category 4 or 5 mammographic assessment or suspicious clinical or ultrasound finding. Interventions  MRI examinations performed prior to breast biopsy; MRI results were interpreted at each site, which were blinded to pathological results. Main Outcome Measures  Area under the receiver operating characteristic curve (AUC), sensitivity, and specificity of breast MRI. Results  Among the 821 patients, there were 404 malignant index lesions, of which 63 were ductal carcinoma in situ (DCIS) and 341 were invasive carcinoma. Of the 417 nonmalignant index lesions, 366 were benign, 47 showed atypical histology, and 4 were lobular carcinoma in situ. The AUC pooled over all institutions was 0.88 (95% confidence interval [CI], 0.86-0.91). MRI correctly detected cancer in 356 of 404 cancer cases (DCIS or invasive cancer), resulting in a sensitivity of 88.1% (95% CI, 84.6%-91.1%), and correctly identified as negative for cancer 281 of 417 cases without cancer, resulting in a specificity of 67.7% (95% CI, 62.7%-71.9%). MRI performance was not significantly affected by mammographic breast density, tumor histology, or menopausal status. The positive predictive values for 356 of 492 patients was 72.4% (95% CI, 68.2%-76.3%) and of mammography for 367 of 695 patients was 52.8% (95% CI, 49.0%-56.6%) (P<.005). Dynamic MRI did not improve the AUC compared with 3-dimensional MRI alone, but the specificity of a washout pattern for 123 of 136 patients without cancer was 90.4% (95% CI, 84%-95%). Conclusions  Breast MRI has high sensitivity but only moderate specificity independent of breast density, tumor type, and menopausal status. Although the positive predictive value of MRI is greater than mammography, MRI does not obviate the need for subsequent tissue sampling in this setting.      

Cataract after glaucoma filtration surgery

PURPOSE: We reviewed the evidence regarding cataract incidence and progression after glaucoma surgery. DESIGN: Evidence-based review of available literature. METHODS: We performed a systematic review of relevant studies published in English. RESULTS: Reports of visually significant cataract after glaucoma surgery are supported by data from randomized clinical trials and large case series. CONCLUSIONS: Patients undergoing glaucoma surgery are at increased risk for the development and progression of cataract.     

Acceleration patterns of the head and pelvis when walking on level and irregular surfaces

The aim of this study was to evaluate acceleration patterns at the head and pelvis while subjects walked on a level and an irregular walking surface, to develop an understanding of how the postural control system responds to challenging walking conditions. Thirty young, healthy subjects walked on a level corridor and on artificial grass underlain with foam and wooden blocks placed in an arbitrary manner. Temporo-spatial gait parameters and acceleration patterns at the head and pelvis were measured. The results revealed that when walking on the irregular surface, subjects were able to maintain their velocity, but adopted a slower and more variable cadence and a significantly longer stride length. The magnitude of pelvis accelerations increased, however head accelerations were not affected by the walking surface. When considered as an overall pattern of movement, these findings suggest that one of the primary objectives of the postural control system when walking on irregular surfaces is head control, and that subjects adapt their stepping pattern on irregular surfaces to ensure that the head remains stable.     

Magnetic Resonance Imaging in Patients Diagnosed With Ductal Carcinoma-In-Situ: Value in the Diagnosis of Residual Disease,Occult Invasion,and Multicentricity

Background: Although magnetic resonance imaging (MRI) has been shown to be a sensitive imaging tool for invasive breast cancers, its utility in ductal carcinoma-in-situ (DCIS) of the breast remains controversial. We studied the performance of MRI in patients with known DCIS for assessment of residual disease, occult invasion, and multicentricity to determine the clinical role of MRI in this setting.Methods: Fifty-one patients with biopsy-proven DCIS underwent contrast-enhanced MRI before surgical treatment. Pre-, early post-, and late postcontrast three-dimensional gradient echo images were obtained and MRI findings were correlated with histopathology. When possible, the performance of MRI and mammography was compared.Results: The accuracy of MRI was 88% in predicting residual disease, 82% in predicting invasive disease, and 90% in predicting multicentricity. The performance of MRI was equivalent in the core biopsy group when compared with the surgical biopsy group. For occult invasion only, MRI and mammography were equivalent. However, overall, MRI was more sensitive and had a higher negative predictive value than mammography.Conclusions:MRI of DCIS can serve as a useful adjunct to mammography by providing a more accurate assessment of the extent of residual or multicentric disease. The performance of MRI is not significantly affected by antecedent surgical excision. MRI may be particularly valuable if preoperatively negative.     

Validation and reproducibility of computerised cell-viability analysis of tissue slices

Background

The identification of live cells using membrane integrity dyes has become a frequently used technique, especially with articular cartilage and chondrocytes in situ where tissue slices are used to assess cell recovery as a function of location. The development of a reproducible computerised method of cell evaluation would eliminate many variables associated with manual counting and significantly reduce the amount of time required to evaluate experimental results.

Methods

To validate a custom computerised counting program, intra-person and inter-person cell counts of nine human evaluators (three groups – unskilled, novice, and experienced) were compared with repeated pixel counts of the custom program on 15 digitised images (in triplicate) of chondrocytes in situ stained with fluorescent dyes.

Results

Results indicated increased reproducibility with increased experience within evaluators [Intraclass Correlation Coefficient (ICC) range = 0.67 (unskilled) to 0.99 (experienced)] and between evaluators [ICC = 0.47 (unskilled), 0.85 (novice), 0.93 (experienced)]. The computer program had perfect reproducibility (ICC = 1.0). There was a significant relationship between the average of the experienced evaluators results and the custom program results (ICC = 0.77).

Conclusions

This study demonstrated that increased experience in cell counting resulted in increased reproducibility both within and between human evaluators but confirmed that the computer program was the most reproducible. There was a good correlation between the intact cell recovery determined by the computer program and the experienced human evaluators. The results of this study showed that the computer counting program was a reproducible tool to evaluate intact cell recovery after use of membrane integrity dyes on chondrocytes in situ. This and the significant decrease in the time used to count the cells by the computer program advocate its use in future studies because it has significant advantages.

     

Knowledge of aging and attitudes toward older people. A survey of Australian podiatric medical students

Podiatric medical students in Australia were surveyed to evaluate their reasons for entering podiatric medicine, knowledge of aging, attitudes toward older people, perceptions of treatment efficacy, and desire to specialize in geriatrics. Few students plan to specialize in geriatrics upon graduation (4%), with most preferring general practice (25%) or sports medicine (21%). However, knowledge of aging was good, and students had favorable attitudes toward older people and considered treatment of older people to be effective. Few age- or gender-related effects were observed. It is concluded that students' lack of desire to specialize in geriatrics may be due not to unfavorable perceptions of older people but rather to the low profile and limited development of geriatrics as a specialty area within the podiatric medical profession.