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1.
Clin Exp Rheumatol ; 2023 Nov 17.
Article in English | MEDLINE | ID: mdl-37976113

ABSTRACT

OBJECTIVES: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) commonly presents with diffuse alveolar haemorrhage (DAH) and/or glomerulonephritis. Patients who present with DAH but without kidney involvement have been understudied. METHODS: Patients with DAH diagnosed by bronchoscopy and attributed to AAV over 8.5 years were retrospectively identified through electronic medical records and bronchoscopy reporting software. Patients with end-stage kidney disease (ESKD) or prior kidney transplant were excluded. Characteristics, treatments, and outcomes were abstracted. RESULTS: 30 patients were identified with DAH secondary to AAV. Five with ESKD or prior kidney transplant, and one with concomitant anti-glomerular basement membrane disease, were excluded, leaving 24 patients for analysis. At the time of qualifying bronchoscopy, six patients had no apparent kidney involvement by AAV, while eight of 18 with kidney involvement required dialysis. Of the eight patients dialysed during the initial hospitalisation, four were declared to have ESKD and three died in the subsequent year (one of whom did both). None of the 16 patients without initial dialysis requirement developed kidney involvement requiring dialysis in the subsequent year, though three of the six without initial evidence of kidney involvement by AAV ultimately developed it. No patient without initial kidney involvement died during follow-up. CONCLUSIONS: In our cohort, patients with DAH due to AAV without initial kidney involvement did not develop kidney involvement requiring dialysis or die during the follow-up period, though half of patients without initial evidence of kidney involvement subsequently developed it. Larger studies are warranted to better characterise this population and guide medical management.

2.
Med Hypotheses ; 82(5): 522-8, 2014 May.
Article in English | MEDLINE | ID: mdl-24581674

ABSTRACT

This hypothesis states that cerebral palsy (CP), autism spectrum disorder (ASD), and attention-deficit/hyperactivity disorder (ADHD) are all caused by an exaggerated central nervous system inflammatory response to a prenatal insult. This prenatal insult may be one or more episodes of ischemia-reperfusion, an infectious disease of the mother or the fetus, or other causes of maternal inflammation such as allergy or autoimmune disease. The resultant fetal inflammatory hyper-response injures susceptible neurons in the developing white matter of the brain in specific areas at specific gestational ages. The exaggerated neuroinflammatory response is theorized to occur between about 19 and 34 post-conception weeks for CP, about 32 and 40 weeks for ADHD, and about 36 and 48 weeks (i.e. 2 months after delivery) for ASD. The exaggerated inflammatory response is hypothesized to occur because present diets limit intake of effective antioxidants and omega-3 polyunsaturated fatty acids while increasing intake of omega-6 polyunsaturated fatty acids. Oxidation products of the omega-3 fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) limit neuroinflammation while oxidation products of the omega-6 fatty acid arachidonic acid exacerbate inflammation. Preventative treatment should begin in all pregnant women during the first trimester and should include both DHA and an effective antioxidant for prevention of neuroinflammation. The suggested antioxidant would be N-acetylcysteine, though melatonin could be chosen instead. Combined DHA and NAC therapy is theorized to decrease the incidence of the three disorders by more than 75%.


Subject(s)
Attention Deficit Disorder with Hyperactivity/prevention & control , Cerebral Palsy/prevention & control , Child Development Disorders, Pervasive/prevention & control , Humans , Models, Theoretical
3.
BMC Pharmacol Toxicol ; 15: 2, 2014 Jan 25.
Article in English | MEDLINE | ID: mdl-24460668

ABSTRACT

BACKGROUND: CLP is an orally administered, non-absorbed, superabsorbent polymer being developed to increase fecal excretion of sodium, potassium and water in patients with heart failure and end-stage renal disease. This study was conducted to evaluate the safety of CLP, and to explore dose-related effects on fecal weight, fecal and urine sodium and potassium excretion, and serum electrolyte concentrations. METHODS: This Phase 1, open-label, dose-escalation study included 25 healthy volunteers, who were administered CLP orally immediately prior to four daily meals for 9 days at doses of 7.5, 15.0, and 25.0 g/day (n = 5/group). An additional dose group received 15.0 g/day CLP under fasting conditions, and an untreated cohort (n = 5) served as control. Twenty-four-hour fecal and urinary output was collected daily. Samples were weighed, and sodium, potassium, and other ion content in stool and urine were measured for each treatment group. Effects on serum cation concentrations, other standard laboratory values, and adverse events were also determined. RESULTS: At doses below 25.0 g/day, CLP was well tolerated, with a low frequency of self-limiting gastrointestinal adverse events. CLP increased fecal weight and fecal sodium and potassium content in a dose-related manner. Concomitant dose-related decreases in urinary sodium and potassium were observed. All serum ion concentrations remained within normal limits. CONCLUSIONS: In this study, oral CLP removed water, sodium and potassium from the body via the gastrointestinal tract in a dose related fashion. CLP could become useful for patients with fluid overload and compromised kidney function in conditions such as congestive heart failure, salt sensitive hypertension, chronic kidney disease and end stage renal disease. TRIAL REGISTRATION: NCT01944007.


Subject(s)
Feces/chemistry , Polymers/administration & dosage , Potassium/metabolism , Sodium/metabolism , Water/metabolism , Adult , Aged , Dose-Response Relationship, Drug , Female , Healthy Volunteers , Humans , Male , Middle Aged , Potassium/urine , Sodium/urine
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