Nonsteroidal anti-inflammatory drug induced duodenal web

Duodenal webs represent an unusual cause of intestinal obstruction in adults. These anomalies are generally considered to be congenital in origin and usually present in infancy. However, they occasionally become symptomatic in adulthood. In these cases, because of the delay in symptoms, the etiology of duodenal webs in adults is uncertain. Gastrointestinal webs in adults have also been reported in the small intestine and colon. It is generally accepted that these lesions are an acquired defect related to long term nonsteroidal anti-inflammatory drug (NSAID) use. We report a patient with a history of long term NSAID use who presented with symptoms of gastric outlet obstruction due to the presence of a duodenal web.     

Nonsteroidal anti-inflammatory drugs and the gut

Aberrant crypt foci (ACF) are putative precursor lesions of colon cancer, recently identified on the methylene blue-stained mucosal surface of human colon. No mutations in K-ras or p53 genes were found by non-radioactive single-strand conformation polymorphism analysis in 14 ACF collected from five patients. Using the more sensitive method of allele-specific polymerase chain reaction (PCR) for K-ras, 8 of 14 ACF were found to contain K-ras mutations, suggesting that mutated cells are present in minute clones in ACF. No dysplasia was observed in any of the ACF containing a mutated clone. The presence of K-ras mutations in ACF suggests that these lesions occur at a very early stage in human colorectal carcinogenesis.     

Nonsteroidal antiinflammatory drug use and reduced risk of large bowel carcinoma

BACKGROUND: Animal experiments and epidemiologic data have suggested that the use of nonsteroidal antiinflammatory drugs (NSAIDs) may decrease the incidence of large bowel carcinoma. Our purpose was to assess the relation of the use of aspirin and nonaspirin NSAIDs with the risk of large bowel carcinoma. METHODS: A population-based case-control study of colon and rectal carcinoma was conducted in Massachusetts from 1992 to 1994. Data on NSAID use and risk factors for large bowel carcinoma were collected by interview from 1201 incident cases of large bowel carcinoma and 1201 controls matched by age, gender, and area of residence. RESULTS: Regular NSAID use that continued into the year before diagnosis was associated with a significantly decreased relative risk estimate overall (0.7; 95% confidence interval [CI], 0.5-0.8) and among Stage II-IV tumors (0.6; 95% CI, 0.4-0.7). There was no reduction in risk for discontinued use. The inverse association with regular continuing use was present across age and gender and for both colon and rectal carcinoma. Similar inverse associations were present for regular continuing use of aspirin and nonaspirin NSAIDs. There was no significant evidence of a trend for the relative risk to decrease as the duration of use increased, nor was there a trend across the dose of aspirin, which ranged from less than one-half of a 325 mg tablet per day to > or = 2 tablets per day. Discontinuation of use in response to symptoms of carcinoma did not appear to explain the inverse association, nor did bias related to diagnosis of the carcinoma. CONCLUSIONS: These data add to the growing body of evidence that suggests a protective effect of NSAIDs against large bowel carcinoma.     

Nonsteroidal anti-inflammatory drugs and severe psychiatric side effects

In the systemic mucopolysaccharidoses (MPS) in animals, corneal clouding resulted from storage of glycosaminoglycans (GAG) in stromal keratocytes. The corneal epithelium was normal (MPS VI and VII) or minimally affected (MPS I), and stromal edema was not a feature even though the corneal endothelium demonstrated variable pathology. The MPS I (cat) cornea showed endothelial cells with large numbers of secondary lysosomal inclusions that were vacuolated or had a granular matrix. The endothelium was uniformly affected, but was not markedly hypertrophied. In contrast, the MPS VI (cat) cornea showed no endothelial cell disease. The MPS VII (dog) cornea had the most significant and dramatic endothelial pathology. The cells were massively hypertrophied and contained large numbers of vacuolated lysosomal inclusions. Regardless of the severity of the morphologic disease, the endothelial cells in these animal models functioned normally in maintaining the relative dehydration of the cornea. The corneal clouding was the result of storage in stromal keratocytes rather than corneal edema from endothelial dysfunction.     

Nonsteroidal anti-inflammatory drugs and corticosteroids for the management of canine osteoarthritis

Anti-inflammatory medications have long been prescribed for relief of the pain and discomfort associated with OA. This occurs despite the recognized side effects associated with use of NSAIDs and corticosteroids. Available evidence suggests that NSAIDs provide this relief through a combination of central and peripheral actions. Recent discovery of two isoforms of cyclooxygenase has increased our understanding of NSAID activity and may result in identification of drugs that potentially will have fewer side effects. A review of NSAIDs used in veterinary medicine indicates that relatively little is known regarding their role in treating OA, although controlled studies involving carprofen and etodolac have increased our knowledge of the efficacy of specific NSAIDs used for this purpose.     

Nonsteroidal anti-inflammatory agents: potential modifiers of periodontal disease progression

The most recent studies of NSAIDs as potential modifiers of periodontal disease progression are reviewed. These studies indicate that NSAIDs have the ability to alter or control the progression of periodontal disease. Reductions in gingival inflammation and in bone loss have been observed following the administration of various NSAIDs. In some cases, bone gain has been achieved. More research is required to determine the possible long-term side effects associated with the chronic usage of NSAIDs, as well as to achieve consensus on the most effective drug for the control of periodontal disease. Until this occurs, and this application of NSAIDs receives government approval, the use of these drugs to control periodontal disease is not recommended.     

Nonsteroidal anti-inflammatory drug-induced enteropathy: case discussion and review of the literature

A computer simulation of a catheter manometer system was used to quantify measurement errors in neonatal blood pressure parameters. Accurate intra-arterial pressure recordings of 21 critically ill newborns were fed into this simulated system. The dynamic characteristics, natural frequency and damping coefficient, were varied from 2.5 to 60 Hz and from 0.1 to 1.4, respectively. As a result, errors in systolic, diastolic and pulse arterial pressure were obtained as a function of natural frequency and damping coefficient. Iso-error curves for 2%, 5% and 10% were constructed. Using these curves, the maximum inaccuracy of any neonatal catheter manometer system can be determined and used in the clinical setting.     

Nonsteroidal anti-inflammatory drugs and bone mineral density in older women: the Rancho Bernardo study

Nonsteroidal anti-inflammatory drugs (NSAIDs) are known to inhibit synthesis of prostaglandins and may help prevent bone loss, but no study has shown the differential association of type or dose of NSAID compound with bone mineral density (BMD). The purpose of this study was to determine the relation of NSAIDs by type and dose to BMD. Participants were 932 Caucasian, community-dwelling women aged 44-98 years from southern California. Data were collected from 1988 to 1991 through the use of standardized medical questionnaires. Medication use was validated by a nurse. BMD at the ultradistal and midshaft radii were measured using single-photon absorptiometry, and at the hip and lumbar spine using dual-energy X-ray absorptiometry. Women (mean age, 72 years) were classified into 818 nonusers and 114 regular daily users of NSAIDs, of which 84 used propionic acid NSAIDs and the remainder used acetic acid NSAIDs. Occasional NSAID users were excluded. Women who used propionic acid NSAIDs, but not acetic acid NSAIDs, had higher BMD at all five sites and significantly higher BMD at the midshaft radius and lumbar spine. These differences remained after controlling for known covariates of osteoporosis. When women with self-reported osteoarthritis were excluded from the model, significantly higher BMD in propionic acid NSAID users was also observed at the femoral neck and total hip. Those who concurrently used estrogen and propionic acid NSAIDs had the highest BMD at all sites, suggesting an additive effect. We conclude that regular daily use of propionic acid NSAIDs, with or without simultaneous use of estrogen, may be helpful in preventing bone loss in older women. However, further research is needed to confirm these results before any clinical practice guidelines can be recommended due to the increased risk of serious complications associated with NSAID use.     

Nonsteroidal anti-inflammatory drugs and cognitive function: do they have a beneficial or deleterious effect?

AIMS/BACKGROUND: A recent advancement in Doppler ultrasonography (US) is power Doppler for detecting low-velocity blood flow at the microvascular level with angle independence. The present study was performed to characterize the factors contributing to the power Doppler signals of hepatocellular carcinoma (HCC). METHOD: Correlation of Doppler signals of HCC in 114 patients with 178 HCC nodules was analyzed in relation to the findings of CT and angiography, tumor characteristics (size, echo pattern, and histological differentiation of tumor), viral markers and severity of liver disease. RESULTS: The sensitivity of power Doppler US was superior to that of CT and angiography (each p<0.05; McNemar's test). The detection rate of power Doppler signal was significantly higher in tumors with diameter > or =2 cm (vs <2 cm in diameter), and with low/mixed echo pattern (vs high echo appearance), and with moderately/poorly differentiated HCC (vs well-differentiated HCC). Univariate analysis revealed that echo pattern, tumor size and histological differentiation of HCC in addition to CT and angiographic findings were significant. Multivariate analysis showed that tumor size and differentiation were significant. CONCLUSION: These results indicate that tumor characteristics play an important role in power Doppler signals and that these could be assessed by the presence or absence of power Doppler signals.     

Alzheimer-type lesions in Huntington's disease

Cognitive changes in Huntington's disease (HD) are variously related to diffuse cortical atrophy with neuron loss and dystrophic neurites leading to disruption of striato-frontal or limbic circuitries, while recent studies suggest an increasing prevalence of Alzheimer-like lesions in HD brain. A comparative morphological study of 27 autopsy cases of HD (age 34 to 75 years) and of 26 age- and sex-matched non-demented controls was performed. Absence of Alzheimer-type lesions was seen in 33% of HD brains (mean age 49 years); 48% showed early non-neuritic tau pathology in limbic areas (Braak stages I and II) without amyloid deposits occurring as early as age 34 years (mean age 54 years), while Braak stages II and III with amyloid plaques were present in 19%, the youngest such HD patient being 42 years (mean age 54 years). In controls, similar tau pathology changes with later onset (age 45 years) and occurrence of amyloid plaques in 26%--all aged over 60 years--were observed. No probable or definite cases of Alzheimer disease (AD) according to CERAD criteria were seen in both cohorts. Those data confirm previous studies on the rare coexistence of HD and AD, although initial stages of Alzheimer-like lesions develop rather early in HD patients, but obviously show less rapid progress even in advanced age. The reasons for the early onset but mild progress of Alzheimer-like lesions in HD and their contribution to cognitive decline await further elucidation.     

Steroid and non-steroidal anti-inflammatory drug therapy of vasculitis

Before corticosteroids were used in the treatment of the systemic necrotizing vasculitides of the polyarteritis nodosa, the disease almost always progressed with variable degree of fulminance leading to death. The use of corticosteroids improves the 5-year survival. The most dramatic break-through in the therapeutic approach to the vasculitides has been clinical experience with cyclophosphamides in treating Wegener's granulomatosis. With this therapeutic regimen, Wegener's granulomatosis can now be considered a curable disease, if treated early and appropriately with therapeutic regimen. These therapeutic strategy can be extended to that of polyarteritis nodosa group of vasculitides. Now, it is clear that cyclophosphamide, either alone or in combination with pre-existing corticosteroid therapy, can effect a dramatic response if instituted early in the course of the disease process. With the advent of deeper insight as to immuno-pathogenesis and pathophysiologic mechanism, the striking therapeutic success can be expected in near future.     

Working memory in Alzheimer-type dementia.

Reviews experimental studies of working memory in dementia of the Alzheimer type (DAT), mainly focusing on investigations using A. D. Baddeley and G. J. Hitch's (1974) working memory model as a framework (e.g., Baddeley, see record 1992-26150-001). These studies show that the articulatory or phonological loop system is intact in early dementia, with a substantial impairment in the central executive system. The neural basis for this impairment is discussed, as are the practical implications of the working memory deficits for the diagnosis and management of Alzheimer's disease (AD). (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The use of digital images in pathology

Many parallel processes occur during the final stages of apoptosis. It is not clear which of these processes occur in all or most models of apoptosis and which occur only in some. In addition, the temporal relationship of these events is not always well understood. Correlated flow cytometric measurements were used to address these questions. Several models of apoptosis were studied, including thymocytes treated with dexamethasone. MOLT-4 cells treated with etoposide, U937 cells treated with anti-Fas, HL-60 cells treated with camptothecin, Raji cells grown in low serum, and aged neutrophils. All models showed a decrease in LDS-751 and fluorescein diacetate (FDA) staining, an increase in staining with dihydrorhodamine 123 (dhR123) or dihydroethidium, and an acidification of the cytoplasm. In each model, these changes were highly correlated, appearing simultaneously as multiparameter measurements. Changes in membrane status detected with merocyanin 540 (MC540) and annexin V behaved differently. A population with LDS-751 and FDA changes but without annexin V or MC540 changes could be demonstrated in some models. Several models did not show any change in annexin V binding, and HL-60 did not show a change in MC540 binding during apoptosis. The loss of cell surface antigens (CD45 and CD16) from aged neutrophils occurred in the entire LDS-751 and FDA dim population, even though other membrane changes (including the appearance of annexin V binding sites) were only apparent in a subset of these cells. These results suggest a model for the ordering of some of the terminal processes in apoptosis, with annexin V and MC540 changes trailing other events in apoptosis. These results confirm the need for caution in using a single-parameter measurement as an indicator of apoptosis for any new model being studied.     

Weight loss in patients with Alzheimer-type dementia

Epidemiologic studies show that weight loss is commonly associated with Alzheimer's disease. It would be a manifestation of the disease itself. It is not easy to explain weight loss as subjects with Alzheimer's disease have adequete caloric intakes. Several hypothesis are considered: increased energy expenditure, biologic disturbances, dysfunction in body weight regulation, mesial cortex temporal atrophy. However, at the present time, no study can give a proper explanation. The amelioration of nutritional problems, which lead to many complications (infections, bedsores, bedridden subjects, etc), could be one of the best strategies to lessen the burden of the disease.     

Nonsteroidal anti-inflammatory drugs increase tumor necrosis factor production in the periphery but not in the central nervous system in mice and rats

Nonsteroidal anti-inflammatory drugs (NSAIDs), which inhibit prostaglandin (PG) synthesis, augment production of tumor necrosis factor (TNF) in most experimental models. We investigated the effect of two NSAIDs, indomethacin and ibuprofen, on the production of TNF in the CNS induced by intracerebroventricular injection of lipopolysaccharide (LPS). Indomethacin and ibuprofen, administered intraperitoneally, augmented (three- to ninefold) the levels of TNF in serum and peripheral organs of mice injected intraperitoneally with LPS and in rats with adjuvant arthritis (up to a sevenfold increase). However, NSAIDs (intraperitoneally or intracerebroventricularly) did not increase brain TNF production induced by intravenous LPS. In fact, indomethacin decreased (1.4-1.8-fold) TNF levels in the spinal cord of rats with experimental autoimmune encephalomyelitis and in the cortex of rats with focal cerebral ischemia. Systemic administration of iloprost inhibited serum TNF levels after intraperitoneal LPS, whereas intracerebroventricular injection of iloprost or PGE2 did not inhibit brain TNF induced by intracerebroventricular LPS. Both peripheral and central TNF productions were inhibited by cyclic AMP level-elevating agents or dexamethasone. Thus, a PG-driven negative feedback controls TNF production in the periphery but not in the CNS.     

Comparative brain pathology of HIV-seronegative and HIV-infected drug addicts

Early stages of infection with human immunodeficiency virus (HIV) were studied in HIV-seropositive drug addicts. Since heroin users are immunocompromized even in the absence of HIV infection, the aim of the present study was to compare the morphological alterations present in HIV-seronegative and HIV-seropositive drug addicts. A total of 60 cases (32 HIV-seronegative subjects, 21 HIV-seropositive patients without signs of acquired immunodeficiency syndrome (AIDS), and 7 HIV-seropositive patients with signs of AIDS) were investigated macroscopically, histologically, and immunohistochemically HIV-seronegative patients presented more frequently with acute drug intoxication, died at a significantly younger age than HIV-seropositive patients, and were found to suffer more frequently from alcohol-related changes. These results indicated that HIV-seronegative and HIV-seropositive patients differed possibly in their drug consumption and also in their general conditions of life. In accordance with previous reports activated microglia and a diffuse astrogliosis in the white matter were detected at a significantly higher frequency and found to be more severe in HIV-seropositive subjects than in HIV-seronegative addicts. A lymphocytic meningitis was present in 6 of 21 HIV-seropositive patients but in none of the HIV-seronegative patients. Perivascular infiltrates consisting of lymphocytes and macrophages were detected at similar frequencies in HIV-seronegative and HIV-seropositive patients but were significantly more severe in patients suffering from lymphocytic meningitis or purulent encephalitis. Opportunistic infections were only demonstrated in 2 AIDS cases. In 10 of the HIV-seronegative patients and in 3 of the HIV-seropositive patients CD68-and Ham56-positive multinucleated cells were detected scattered in the subarachnoidal space exclusively over the frontal cortex.     

Neutrophils, Helicobacter pylori, and nonsteroidal anti-inflammatory drug ulcers

BACKGROUND & AIMS: Gastric injury by nonsteroidal anti-inflammatory drugs (NSAIDs) is minimal in neutropenic animals. This study examined peptic ulcer development in the presence or absence of gastric neutrophils in patients requiring long-term use of NSAIDs. METHODS: Gastric histology, neutrophils, and Helicobacter pylori were assessed in 120 patients randomized to receive placebo or 20 or 40 mg famotidine twice daily as prophylaxis against NSAID-related ulcers and who underwent endoscopy at 0, 4, 12, and 24 weeks. RESULTS: In 43 patients without gastric neutrophils, ulcers developed in 1 of 14 (7.7%) taking placebo, 2 of 16 (12.5%) taking 20 mg famotidine, and none of 13 taking 40 mg famotidine. However, in 77 patients with neutrophils, ulcers developed in 13 of 28 (47. 4%) taking placebo (P < 0.001), 3 of 26 (12.6%) taking 20 mg famotidine, and 3 of 23 (13%) taking 40 mg famotidine. Eight of 46 patients (17%) without H. pylori had neutrophils compared with 69 of 74 (93%) with both H. pylori and neutrophils (P < 0.001). CONCLUSIONS: Gastric neutrophils increase the incidence of ulceration in long-term NSAID users. Because neutrophils exist with H. pylori, eradicating this infection might prevent NSAID-related peptic ulcers.