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Biomedical subjects

B R Leaker

Publications and source records attributed to B R Leaker.

11 recordsLinked to original sources
PubMed2006

Effects of a reversible beta-tryptase and trypsin inhibitor (RWJ-58643) on nasal allergic responses.

BACKGROUND: beta-Tryptase is a multifunctional mast cell serine protease released during mast cell degranulation and tryptase/trypsin inhibitors are a novel potential therapeutic approach for allergic inflammatory diseases. OBJECTIVES: This study was performed to assess the effects of RWJ-58643 on nasal symptoms, eosinophil influx, and cytokine and chemokine release following nasal allergen challenge (NAC). METHODS: Male patients with grass pollen allergic rhinitis (n=16) out of season received single doses of RWJ-58643 (100, 300, 600 microg) or matched placebo given 30 min before NAC in a double-blind, randomized crossover design. A single dose of 200 microg budesonide was studied in an open-label extension phase. NAC was performed with Timothy grass pollen (ALK) via a nasal device, and nasal lavage was performed at times 0 (pre-drug, pre-allergen), 0.5 (30 min post-drug, pre-NAC) 1.5, 2.5, 4.5, 6.5, 8.5, and 24 h after drug administration. Nasal lavage mediators were analysed using a sensitive multiplexed bead immunoassay system. RESULTS: Low-dose RWJ-58643 (100 microg) and budesonide (200 microg) significantly reduced symptoms, eosinophils and levels of IL-5 following NAC. However, higher doses of RWJ-58643 (300 and 600 microg) caused a late eosinophilia and preceding increases in IL-5 compared with placebo. CONCLUSIONS: This study suggests that combined beta-tryptase and trypsin inhibition has therapeutic potential in allergic inflammation, however, this property is dose responsive and higher doses are ineffective and may cause eosinophilia.

Administration, Intranasal↗
PubMed2005

Single dose topical corticosteroid inhibits IL-5 and IL-13 in nasal lavage following grass pollen challenge.

BACKGROUND: Nasal lavage is a noninvasive method of obtaining inflammatory exudates following nasal allergen challenge (NAC), and permits cells and released mediators to be evaluated. OBJECTIVE: To determine the effects of a single dose of topical steroid on eosinophils and levels of chemokines and cytokines in nasal lavage fluid following NAC in patients with allergic rhinitis. METHODS: Patients with grass pollen seasonal allergic rhinitis (n = 32) out of the allergy season received either nasal budesonide (100 microg per nostril) or matched placebo before allergen challenge in a double blind two-way crossover design. A semi-automated mixed bead array system was employed to measure multiple chemokines and cytokines in small volumes (50 microl) of nasal lavage supernatants. RESULTS: Following NAC there was a rapid onset of nasal symptoms together with nasal eosinophilia, and the appearance of IL-5 and IL-13 in lavages between 4 and 8 h. Elevated levels of eotaxin, RANTES, IL-8 and MCP-1 were also detected following allergen challenge. A single dose of nasal budesonide caused a decrease in symptoms (P < 0.05) and nasal eosinophils (P < 0.05) with selective abrogation of IL-5 and IL-13 responses (P < 0.05), but a lack of effect on levels of eotaxin, RANTES, IL-8 and MCP-1. CONCLUSION: This study suggests that a single dose of nasal steroid has the capacity to selectively abolish IL-5 and IL-13 responses following NAC. This model should be convenient for testing novel anti-inflammatory and immunoregulatory agents intended for the treatment of allergic rhinitis.

Administration, Intranasal↗
PubMed1995

Loin pain and haematuria syndrome: a somatoform disorder.

Fifteen patients with the loin pain and haematuria syndrome (LPH) were compared with 10 patients with complicated renal stone disease referred to the same tertiary centre and matched for age, sex and duration of illness. LPH patients had a history of three times more medically unexplained somatic symptoms other than loin pain (p < 0.01) and a higher proportion took analgesics regularly (p < 0.01). The onset of pain was associated with an adverse psychologically important life-event in eight of the LPH patients but in none of the controls (p < 0.02). LPH patients more frequently recalled serious parental illness and disability in childhood (p < 0.001) than controls, and a higher proportion felt responsible for causing or alleviating parental illness or distress (p < 0.05). LPH subjects scored higher in the 'paternal care' dimension of the Parental Bonding Instrument (p < 0.05). No difference was found between LPH patients and controls in terms of current depression and anxiety but both groups exhibited high rates of lifetime depression. LPH patients expressed lower levels of anger and hostility (p < 0.002) than did controls. Our observations suggest that psychological factors are of major importance in the aetiology of LPH, which may represent a type of somatoform pain disorder.

Adult↗
PubMed1991

Haemostatic activation and proteinuria as factors in the progression of chronic renal failure.

Haemostatic activation was measured in patients with either non-diabetic chronic renal failure (CRF) or diabetic nephropathy. We have investigated the relationship between these haemostatic markers and the rate of progression of renal failure. When compared with age- and sex-matched healthy controls, both patient groups showed significantly elevated plasma concentrations of D dimer, von Willebrand factor antigen (vWFAg), and C-reactive protein (CRP) (all P less than 0.001), as well as an increase in spontaneous platelet aggregation (P less than 0.01). Plasma concentration of platelet factor 4 was slightly but not significantly increased. Serum thromboxane was subnormal (P less than 0.01). Multiple regression analysis showed that in non-diabetic CRF proteinuria and serum TxB2 were independently related to the rate of progression of renal failure; in diabetic nephropathy proteinuria and vWFAg were independently related to the rate of progression. In both groups the relationship was stronger with proteinuria (standardised regression coefficients 0.56 and 0.45 respectively) than with serum TxB2 (0.29) or with vWFAg (0.37). We have found haemostatic activation in both non-diabetic and diabetic progressive renal failure. Proteinuria, and also in this study serum TxB2 and vWFAg, appear to be determining factors in the progression of renal failure, and their measurement may have prognostic value.

Adolescent↗
PubMed1991

Accuracy of reagent strip testing for urinary tract infection in the elderly.

The accuracy of reagent strip testing for urinary tract infection (UTI) was assessed in 100 elderly patients (50 acute patients admitted to hospital and 50 attending the day hospital). Reagent strip sensitivities were: acute patients-urinary nitrite 83%, blood 67%, protein 72% and leucocytes 72%, and day hospital patients-urinary nitrite 90%, blood 65%, protein 30% and leucocytes 60%. Urinary nitrite specificities were 100% for both groups of patients. Only 28% of patients with a UTI had specific symptoms of the infection; pyrexia and a raised WBC also proved poor indicators. Urinary nitrite was thus the most accurate immediate indicator of UTI.

Aged↗
PubMed1990

Haemostatic changes in the loin pain and haematuria syndrome: secondary to renal vasospasm?

Twenty-five patients (seven male, 18 female) were diagnosed as having the loin pain and haematuria syndrome. Presenting symptoms were either loin pain alone or pain associated with macroscopic or microscopic haematuria, and were longstanding, having been present for mean of 9.3 years in males, and 10 years in females. Ten patients described symptoms of passing gravel or renal stones but these were only demonstrated radiologically in two patients. Investigation of all patients showed anatomically normal renal tracts, normal renal function, and no significant proteinuria. Phase-contrast microscopy during episodes of haematuria revealed dysmorphic red cells in all 10 patients studied. Renal biopsies were performed in 20 patients and showed no glomerular pathology, but arteriolar and arterial hyalinosis was seen in 13 of 20 (65 per cent), fibro-elastosis in larger vessels in eight of 20 (40 per cent) and red blood cells in tubules in 13 of 20 (65 per cent) patients. The histological appearance in vessels was similar to that seen in cyclosporin A nephrotoxicity and would be consistent with the hypothesis that regional vasospasm occurs in the cortical circulation. Haematological studies in 22 patients, when compared with age and sex matched controls, showed the presence of circulating platelet aggregates, elevation of plasma beta-thromboglobulin (p less than 0.001), and increased platelet aggregation in response to serotonin and ADP (p less than 0.05 and p less than 0.03, respectively). Plasma concentrations of D dimer (p less than 0.02) and C-reactive protein (p less than 0.03) were also significantly elevated in the patient group. There was no deterioration of renal function during a mean observation period of 3.7 years and no patients developed proteinuria. Treatment was largely supportive; seven patients with intractable loin pain underwent surgical denervation with the relief of pain in four.

Adult↗
PubMed1986

Rapid improvement in severe lupus glomerular lesions following intensive plasma exchange associated with immunosuppression.

We report our experience of intensive plasma exchange (PE) in the treatment of 12 females with severe diffuse proliferative lupus nephritis. All had active disease with crescentic lesions demonstrated on biopsy immediately before PE. Nine patients were also treated with high dose steroids, three patients with low dose steroids and most patients also received cytotoxic therapy. Eight of the 12 patients were biopsied immediately after a course of PE. All but one patient (low dose steroid group) showed considerable diminution of histologic activity with resolution of crescentic lesions. Plasma exchange may accelerate such resolution over conventional therapy, prevent subsequent sclerosis and preserve functional renal tissue.

Adolescent↗
PubMed1986

Triamterene-induced crystalluria and cylinduria: clinical and experimental studies.

We examined the occurrence of crystals and casts in the urine of healthy subjects after administration of triamterene and the site of crystal formation in experimental animals. Twenty out of twenty healthy subjects had abundant triamterene crystals and casts in acid urine after receiving a single 100 mg dose. Casts were present in the urine from 2-11 hours after administration of the diuretic. Cast formation occurred in acidic urine and was prevented by alkalinization of the urine with potassium citrate. Animal studies showed that crystallization and cast formation occurred in the medullary and papillary collecting ducts of the rat kidney. These findings provide a possible explanation for the reported nephrotoxicity of triamterene, particularly when given to patients who are receiving non-steroidal anti-inflammatory agents.

Adult↗