Mannitol and frusemide in the treatment of diuretic resistant oedema in nephrotic syndrome.
(25/2723)
Three children (two girls aged 7 and 9 years, and one boy aged 4 years) with diuretic resistant oedema in steroid resistant nephrotic syndrome were treated with a combination of intravenous mannitol and frusemide. All three responded with loss of oedema of 10% to 30% of body weight over one week. There were no complications of hypertension or hypovolaemia. Mannitol-frusemide combination is a safe, inexpensive, and effective treatment for diuretic resistant oedema. Its use in other conditions and in developing countries (where the availability and purity of 20% albumin is limited) needs to be explored. (+info)
Oedema in the lower limb of patients with chronic critical limb ischaemia (CLI).
(26/2723)
OBJECTIVE: approximately 70% of patients with chronic critical limb ischaemia (CLI) show clinical signs of oedema in the distal leg and foot. The primary aim of the present investigation was to quantify this oedema. In addition we investigated whether oedema formation could be due to deep venous thrombosis (DVT). METHODS: fifteen patients with unilateral CLI and oedema were studied, four males and 11 females, with a mean age of 77+/-10.3 years. Water displacement volumetry (WDV) was used to measure limb volume. Colour duplex ultrasound (CDU) and venous occlusion plethysmography (VOP) were applied to exclude functionally significant DVT. Blood chemistry was analysed to screen for some causative factors of generalised oedema formation. RESULTS: the mean volume of the limbs with CLI was 9% greater than the contralateral limbs (1279+/-325 ml vs. 1179+/-298 ml). None of the patients had functionally significant DVT. The mean plasma albumin concentration was reduced at 28.5+/-6.6 g/l. CONCLUSION: a significantly reduced plasma albumin concentration cannot be regarded as a causative factor, since the oedema is unilateral. The aetiology of oedema formation is probably multifactorial, and further investigations are under progress to elucidate relevant pathogenetic factors. (+info)
Causal pathways for incident lower-extremity ulcers in patients with diabetes from two settings.
(27/2723)
OBJECTIVE: To determine the frequency and constellations of anatomic, pathophysiologic, and environmental factors involved in the development of incident diabetic foot ulcers in patients with diabetes and no history of foot ulcers from Manchester, U.K., and Seattle, Washington, research settings. RESEARCH DESIGN AND METHODS: The Rothman model of causation was applied to the diabetic foot ulcer condition. The presence of structural deformities, peripheral neuropathy, ischemia, infection, edema, and callus formation was determined for diabetic individuals with incident foot ulcers in Manchester and Seattle. Demographic, health, diabetes, and ulcer data were ascertained for each patient. A multidisciplinary group of foot specialists blinded to patient identity independently reviewed detailed abstracts to determine component and sufficient causes present and contributing to the development of each patient's foot ulcer. A modified Delphi process assisted the group in reaching consensus on component causes for each patient. Estimates of the proportion of ulcers that could be ascribed to each component cause were computed. RESULTS: From among 92 study patients from Manchester and 56 from Seattle, 32 unique causal pathways were identified. A critical triad (neuropathy, minor foot trauma, foot deformity) was present in > 63% of patient's causal pathways to foot ulcers. The components edema and ischemia contributed to the development of 37 and 35% of foot ulcers, respectively. Callus formation was associated with ulcer development in 30% of the pathways. Two unitary causes of ulcer were identified, with trauma and edema accounting for 6 and < 1% of ulcers, respectively. The majority of the lesions were on the plantar toes, forefoot, and midfoot. CONCLUSIONS: The most frequent component causes for lower-extremity ulcers were trauma, neuropathy, and deformity, which were present in a majority of patients. Clinicians are encouraged to use proven strategies to prevent and decrease the impact of modifiable conditions leading to foot ulcers in patients with diabetes. (+info)
Effect of locoweed (Astragalus ientiginosus) feeding of fetal lamb development.
(28/2723)
Locoweed, Astragalus lentiginosus, was fed to pregnant ewes for various periods during gestation. The principal gross effects on the developing fetuses were observed to be delayed placentation, decreased vascularization, fetal edema and hemorrhage, and alteration of cotyledon development. Deformed lambs and undersized lambs also occurred. Data from sheep fed locoweed during various periods of the entire gestation period are summarized and indicate that locoweed poisoning in the fetus as with the adult is a chronic type of intoxication. Also, poisoning of the fetus parallels poisoning in the dam. (+info)
Development of a flow cytometry assay for the identification and differentiation of chemicals with the potential to elicit irritation, IgE-mediated, or T cell-mediated hypersensitivity responses.
(29/2723)
These studies were conducted to investigate the potential use of a flow cytometric analysis method for the identification and differentiation of chemicals with the capacity to induce irritation, IgE- or T cell-mediated hypersensitivity responses. An initial study investigated the ability of equally sensitizing concentrations (determined by local lymph node assay) of IgE-mediated (Toluene Diisocyanate-TDI) and T cell-mediated (Dinitrofluorobenzene-DNFB) allergens to differentially modulate the IgE+B220+ population in the lymph nodes draining the dermal exposure site. Sodium lauryl sulfate (SLS) was also tested as a nonsensitizing irritant control. Female B6C3F1 mice were dermally exposed once daily for 4 consecutive days, with the optimum time point for analysis determined by examining the IgE+B220+ population 8, 10, and 12 days post-initial chemical exposure. At the peak time point, day 10, the IgE+B220+ population was significantly elevated in TDI (41%), while moderately elevated in DNFB (18%) exposed animals when compared to the vehicle (0.8%), and remained unchanged in SLS (2.2%) exposed animals when compared to the ethanol control (2.5%). Experiments in our laboratory and others have demonstrated that the draining lymph node B220+ population becomes significantly elevated following exposure to allergens (IgE- and T cell-mediated), not irritants, allowing for their differentiation. An existing mouse ear swelling assay was used to identify chemical irritants. Therefore, using the endpoints of percent ear swelling, percent B220+ cells, and percent IgE+B220+ cells, a combined irritancy/phenotypic analysis assay was developed and tested with tetradecane (irritant), toluene diisocyanate, trimellitic anhydride (IgE-mediated allergens), benzalkonium chloride, dinitrofluorobenzene, oxazolone, and dinitrochlorobenzene (T cell-mediated allergens) over a range of concentrations. Based upon the pattern of response observed, a paradigm was developed for continued evaluation: Irritant exposure will result in significant ear swelling without altering the B220+ or IgE+B220+ populations. Exposure to sensitizers (IgE-mediated or T cell-mediated) will increase the B220+ population and the percent ear swelling will remain unchanged or will significantly increase, depending on the irritancy capacity of the chemical. Both the IgE+B220+ and B220+ populations will become elevated at the same test concentration following exposure to IgE-mediated, hypersensitivity inducing allergens. At its peak, the percent of IgE+B220+ cells will be equal to the percent of B220+ cells. The B220+ population will increase at a lower test concentration than the IgE+B220+ population, following exposure to T cell-mediated, hypersensitivity inducing allergens. At its peak, the percent of IgE+B220+ cells will reach less than half that of the percent of B220+ cells. The irritancy/phenotypic analysis method may represent a single murine assay able to identify and differentiate chemicals with the capacity to induce irritation, or IgE-mediated or T cell-mediated responses. (+info)
Comparison of in vitro and in vivo human skin responses to consumer products and ingredients with a range of irritancy potential.
(30/2723)
Human skin equivalent cultures were investigated as possible pre-clinical skin irritation screens to aid safety assessments for chemicals and product formulations, and to facilitate design of safe and efficient human studies. In vitro responses in human skin equivalent cultures were compared directly to in vivo human skin responses from historic or concurrent skin tests for representative chemicals and products, including surfactants, cosmetics, antiperspirants, and deodorants. The in vivo data consisted of visual scores (i.e., erythema and edema) from skin-patch tests and diary accounts of skin irritation from product-use studies. In the in vitro studies, cornified, air-interfaced human skin cultures (EpiDerm) were evaluated using methods designed to parallel human clinical protocols with topical dosing of neat or diluted test substances to the stratum corneum surface of the skin cultures. The in vitro endpoints have previously been shown to be relevant to human skin irritation in vivo, including the MTT metabolism assay of cell viability, enzyme release (lactate dehydrogenase and aspartate aminotransferase), and inflammatory cytokine expression (Interleukin-1alpha). For surfactants, dose-response curves of MTT cell-viability data clearly distinguished strongly-irritating from milder surfactants and rank-ordered irritancy potential in a manner similar to repeat-application (3x), patch-test results. For the antiperspirant and deodorant products, all the in vitro endpoints correlated well with consumer-reported irritation (r, 0.75-0.94), with Interleukin-1alpha (IL-1alpha) release, showing the greatest capacity to distinguish irritancy over a broad range. IL-1alpha release also showed the best prediction of human skin scores from 14-day cumulative irritancy tests of cosmetic products. These results confirm the potential value of cornified human skin cultures as in vitro pre-clinical screens for prediction of human skin irritation responses. A preliminary report of these results has been published. (+info)
[Arg6,D-Trp7,9,NmePhe8]-substance P (6-11) activates JNK and induces apoptosis in small cell lung cancer cells via an oxidant-dependent mechanism.
(31/2723)
[Arg6,D-Trp7,9,NmePhe8]-substance P (6-11) (antagonist G) is a novel class of anti-cancer agent that inhibits small-cell lung cancer (SCLC) cell growth in vitro and in vivo and is entering phase II clinical investigation for the treatment of SCLC. Although antagonist G blocks SCLC cell growth (IC50 = 24.5 +/- 1.5 and 38.5 +/- 1.5 microM for the H69 and H510 cell lines respectively), its exact mechanism of action is unclear. This study shows that antagonist G stimulates apoptosis as assessed by morphology (EC50 = 5.9 +/- 0.1 and 15.2 +/- 2.7 microM for the H69 and H510 cell lines respectively) and stimulates c-jun-N-terminal kinase (JNK) activity in SCLC cells (EC50 = 3.2 +/- 0.1 and 15.2 +/- 2.7 microM). This activity is neuropeptide-independent, but dependent on the generation of reactive oxygen species (ROS) and is inhibited by the free radical scavenger n-acetyl cysteine. Furthermore, antagonist G itself induces inflammation (59% increase in oedema volume compared to control) and potentiates (by 35-40%) bradykinin-induced oedema formation in vivo. In view of these results we show that, as well as acting as a 'broad-spectrum' neuropeptide antagonist, antagonist G stimulates basal G-protein activity in SCLC cell membranes (81 +/- 12% stimulation at 10 microM), thereby displaying a unique ability to stimulate certain signal transduction pathways by activating G-proteins. This novel activity may be instrumental for full anti-cancer activity in SCLC cells and may also account for antagonist G activity in non-neuropeptide-dependent cancers. (+info)
Remitting seronegative symmetrical synovitis with pitting oedema (RS3PE) syndrome: a prospective follow up and magnetic resonance imaging study.
(32/2723)
OBJECTIVE: To determine the clinical characteristics of patients with "pure" remitting seronegative symmetrical synovitis with pitting oedema (RS3PE) syndrome, and to investigate its relation with polymyalgia rheumatica (PMR). Magnetic resonance imaging (MRI) was used to describe the anatomical structures affected by inflammation in pure RS3PE syndrome. METHODS: A prospective follow up study of 23 consecutive patients with pure RS3PE syndrome and 177 consecutive patients with PMR diagnosed over a five year period in two Italian secondary referral centres of rheumatology. Hands or feet MRI, or both, was performed at diagnosis in 7 of 23 patients. RESULTS: At inspection evidence of hand and/or foot tenosynovitis was present in all the 23 patients with pure RS3PE syndrome. Twenty one (12%) patients with PMR associated distal extremity swelling with pitting oedema. No significant differences in the sex, age at onset of disease, acute phase reactant values at diagnosis, frequency of peripheral synovitis and carpal tunnel syndrome and frequency of HLA-B7 antigen were present between patients with pure RS3PE and PMR. In both conditions no patient under 50 was observed, the disease frequency increased significantly with age and the highest frequency was present in the age group 70-79 years. Clinical symptoms for both conditions responded promptly to corticosteroids and no patient developed rheumatoid arthritis during the follow up. However, the patients with pure RS3PE syndrome were characterised by shorter duration of treatment, lower cumulative corticosteroid dose and lower frequency of systemic signs/symptoms and relapse/recurrence. Hands and feet MRI showed evidence of tenosynovitis in five patients and joint synovitis in three patients. CONCLUSION: The similarities of demographic, clinical, and MRI findings between RS3PE syndrome and PMR and the concurrence of the two syndromes suggest that these conditions may be part of the same disease and that the diagnostic labels of PMR and RS3PE syndrome may not indicate a real difference. The presence of distal oedema seems to indicate a better prognosis. (+info)