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1.
Clin Exp Immunol ; 160(3): 340-7, 2010 Jun.
Article in English | MEDLINE | ID: mdl-20345981

ABSTRACT

Human endogenous retroviruses (HERVs) are remnants of ancient retroviral infections within the human genome. These molecular fossils draw parallels with present-day exogenous retroviruses and have been linked previously with immunopathology within rheumatoid arthritis (RA). Mechanisms of pathogenesis for HERV-K in RA such as molecular mimicry were investigated. To clarify a role for HERVs in RA, potential autoantigens implicated in autoimmunity were scanned for sequence identity with retroviral epitopes. Short retroviral peptides modelling shared epitopes were synthesized, to survey anti-serum of RA patients and disease controls. A novel real-time polymerase chain reaction (PCR) assay was also developed to quantify accurately levels of HERV-K (HML-2) gag expression, relative to normalized housekeeping gene expression. Both serological and molecular assays showed significant increases in HERV-K (HML-2) gag activity in RA patients, compared to disease controls. The real-time PCR assay identified significant up-regulation in HERV-K mRNA levels in RA patients compared to inflammatory and healthy controls. Exogenous viral protein expression and proinflammatory cytokines were also shown to exert modulatory effects over HERV-K (HML-2) transcription. From our data, it can be concluded that RA patients exhibited significantly elevated levels of HERV-K (HML-2) gag activity compared to controls. Additional factors influencing HERV activity within the synovium were also identified. The significant variation in RA patients, both serologically and transcriptionally, may be an indication that RA is an umbrella term for a number of separate disease entities, of which particular HERV polymorphisms may play a role in development.


Subject(s)
Arthritis, Rheumatoid/metabolism , Autoantigens/metabolism , Endogenous Retroviruses/metabolism , Gene Expression Regulation, Viral/immunology , Gene Products, gag/biosynthesis , Molecular Mimicry , Peptides/metabolism , Adult , Aged , Arthritis, Rheumatoid/immunology , Arthritis, Rheumatoid/pathology , Arthritis, Rheumatoid/virology , Autoantigens/immunology , Endogenous Retroviruses/immunology , Epitopes/immunology , Epitopes/metabolism , Female , Gene Products, gag/immunology , Humans , Male , Middle Aged , Peptides/immunology , Polymorphism, Genetic/immunology , RNA, Messenger/biosynthesis , RNA, Messenger/immunology , RNA, Viral/biosynthesis , RNA, Viral/immunology , Synovial Membrane/immunology , Synovial Membrane/metabolism , Synovial Membrane/virology , Transcription, Genetic/immunology
2.
QJM ; 101(2): 155-8, 2008 Feb.
Article in English | MEDLINE | ID: mdl-18194976

ABSTRACT

A formula derived from the Modification of Diet in Renal Disease (MDRD) study in chronic renal disease is widely used to estimate glomerular filtration rate (GFR). Recently a ten-year follow-up of MDRD participants evaluated four tests of kidney function measured at baseline as predictors of important long-term clinical outcomes. Surprisingly, neither formula-estimated GFR nor reference method GFR showed a clear advantage over simple creatinine measurement whereas another test, cystatin C, looked more promising. This raises important points of principle in terms of how the usefulness of test strategies should be assessed. Data on clinical outcomes are an essential ingredient in this process.


Subject(s)
Feeding Behavior , Glomerular Filtration Rate/physiology , Kidney Diseases/diet therapy , Outcome Assessment, Health Care/standards , Chronic Disease , Creatinine/blood , Cystatin C , Cystatins/blood , Feeding Behavior/physiology , Follow-Up Studies , Humans , Kidney Diseases/blood , Kidney Diseases/physiopathology , Kidney Function Tests/methods
3.
Clin Nephrol ; 58(3): 244-6, 2002 Sep.
Article in English | MEDLINE | ID: mdl-12356196

ABSTRACT

A 47-year-old dialysis patient developed severe sclerosing peritonitis. The patient has been unable to take any nutrition by mouth for 27 months. She has been maintained daily on home parenteral nutrition and hemodialysis 3 times per week. It has been possible for her to have a good quality of life and to maintain good nutritional status.


Subject(s)
Parenteral Nutrition, Home Total , Peritoneal Dialysis, Continuous Ambulatory/adverse effects , Peritonitis/etiology , Female , Humans , Kidney Failure, Chronic/therapy , Middle Aged , Peritonitis/therapy , Quality of Life , Renal Dialysis , Sclerosis
4.
Lancet ; 343(8899): 734, 1994 Mar 19.
Article in English | MEDLINE | ID: mdl-7907704
6.
Nephrol Dial Transplant ; 6(1): 21-6, 1991.
Article in English | MEDLINE | ID: mdl-2057112

ABSTRACT

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.


Subject(s)
Hemostasis/physiology , Kidney Failure, Chronic/etiology , Proteinuria/complications , Adolescent , Adult , Aged , Antigens/blood , Diabetic Nephropathies/blood , Diabetic Nephropathies/etiology , Diabetic Nephropathies/physiopathology , Female , Glomerulosclerosis, Focal Segmental/blood , Glomerulosclerosis, Focal Segmental/etiology , Glomerulosclerosis, Focal Segmental/physiopathology , Humans , Kidney/physiopathology , Kidney Failure, Chronic/blood , Kidney Failure, Chronic/physiopathology , Male , Middle Aged , Platelet Activation , Thromboxane B2/blood , von Willebrand Factor/immunology
7.
Diabet Med ; 7(10): 880-6, 1990 Dec.
Article in English | MEDLINE | ID: mdl-2149685

ABSTRACT

Blood rheology was investigated in patients with diabetic nephropathy and progressive renal insufficiency, and compared with similar non-diabetic patients and healthy control subjects. Plasma viscosity and whole blood viscosity at standardized haematocrit were elevated to a comparable degree in the two patient groups, but erythrocyte deformability was normal. In diabetic patients, the rate of progression of renal failure showed weak, but significant, correlations with plasma viscosity (rs = 0.50, p = 0.005), standardized whole blood viscosity (rs = 0.41, p = 0.021), plasma fibrinogen (rs = 0.46, p = 0.010), C reactive protein (rs = 0.40, p = 0.023), and proteinuria (rs = 0.52, p = 0.003). Both plasma viscosity and plasma fibrinogen correlated significantly with proteinuria (rs = 0.45, p = 0.012 and 0.40, p = 0.027, respectively). Rheological abnormality is probably a manifestation of increased acute phase proteins, but it remains to be determined whether these are the cause or the effect of the renal injury. Abnormal blood rheology may be a risk factor for the progression of renal failure in diabetic nephropathy.


Subject(s)
Blood Viscosity , Diabetic Nephropathies/physiopathology , Kidney Failure, Chronic/physiopathology , Adult , Diabetic Nephropathies/blood , Female , Humans , Kidney Failure, Chronic/blood , Kidney Failure, Chronic/etiology , Kidney Function Tests , Male , Middle Aged , Proteinuria , Reference Values , Rheology
8.
Clin Intensive Care ; 1(6): 268-73, 1990.
Article in English | MEDLINE | ID: mdl-10149094

ABSTRACT

Mortality from acute renal failure (ARF) remains very high and is associated with the development of multisystem failure. Technical developments in haemodialysis machines and dialyser membranes have reduced complications associated with haemodialysis. However, some patients are too unstable to be haemodialysed successfully. Continuous haemofiltration and continuous arterio-venous (or veno-venous) haemodialysis can be performed on Intensive Care Units in hospitals without the availability of a Renal Unit. These techniques provide more effective and controlled removal of fluid and uraemic toxins. There are now few indications for the use of peritoneal dialysis. These new developments have facilitated easier management of the unstable patient with acute renal failure. Whether the prognosis of acute renal failure patients will be improved remains to be determined.


Subject(s)
Acute Kidney Injury/therapy , Hemofiltration/methods , Peritoneal Dialysis/methods , Renal Dialysis/methods , Acute Kidney Injury/etiology , Anticoagulants/therapeutic use , Catheters, Indwelling , Humans , Intensive Care Units
9.
Thromb Haemost ; 61(3): 522-5, 1989 Jun 30.
Article in English | MEDLINE | ID: mdl-2799764

ABSTRACT

D dimer and other large fragments produced during the breakdown of crosslinked fibrin may be measured by enzyme immunoassay using monoclonal antibodies. In 91 patients with renal disease and varying degrees of renal dysfunction, plasma D dimer showed no correlation with renal function, whereas FgE antigen, a fibrinogen derivative which is known to be cleared in part by the kidney, showed a significant negative correlation with creatinine clearance. Plasma concentrations of D dimer were, however, increased in patients with chronic renal failure (244 +/- 31 ng/ml) (mean +/- SEM) and diabetic nephropathy (308 +/- 74 ng/ml), when compared with healthy controls (96 +/- 13 ng/ml), and grossly elevated in patients with acute renal failure (2,451 +/- 1,007 ng/ml). The results indicate an increase in fibrin formation and lysis, and not simply reduced elimination of D dimer by the kidneys, and are further evidence of activated coagulation in renal disease. D dimer appears to be a useful marker of fibrin breakdown in renal failure.


Subject(s)
Fibrin Fibrinogen Degradation Products/analysis , Kidney Diseases/blood , Biomarkers/blood , Creatinine/blood , Creatinine/urine , Humans , Kidney Diseases/physiopathology , Kidney Failure, Chronic/blood , Kidney Failure, Chronic/physiopathology , Kidney Function Tests , Molecular Weight , Platelet Factor 4/analysis
10.
Nephrol Dial Transplant ; 4(5): 366-71, 1989.
Article in English | MEDLINE | ID: mdl-2505187

ABSTRACT

Weakness in haemodialysis patients has been attributed to several factors including carnitine deficiency. Malnutrition, neuropathy, uraemic myopathy and parathyroid hormone excess may all be important. Six haemodialysis patients were shown to have reduced muscle power compared with a normal population, and to be malnourished by dietary assessment, and features of their weakness were investigated. Total carnitine was normal in plasma but elevated in muscle, with an excess of esterified carnitine in both plasma and muscle and diminished free plasma carnitine. Muscle biopsy showed no features of carnitine deficiency and electromyography showed a non-specific neuropathy with additional myopathic changes in some. Dietary supplementation with L-carnitine (2 g/day) for 6 weeks in a placebo-controlled trial showed a redistribution of carnitine fractions but no subjective or objective improvement in muscle function. There was no improvement in the plasma lipid profile. The weakness of haemodialysis patients is multifactorial. We have not demonstrated total carnitine depletion in either muscle or plasma, and oral supplementation of L-carnitine has no demonstrable effect in this group.


Subject(s)
Carnitine/deficiency , Kidney Failure, Chronic/blood , Muscle Hypotonia/blood , Renal Dialysis , Administration, Oral , Biopsy , Carnitine/administration & dosage , Electromyography , Female , Humans , Isometric Contraction/drug effects , Male , Middle Aged , Muscle Hypotonia/therapy , Muscles/pathology , Muscular Atrophy/blood
11.
Thromb Haemost ; 60(1): 83-7, 1988 Aug 30.
Article in English | MEDLINE | ID: mdl-3187950

ABSTRACT

Bleeding time and platelet function tests were performed on 31 patients with progressive chronic renal failure (CRF) due to non-immunological (urological) causes, and compared with 22 healthy controls. Patients were classified as mild (plasma creatinine less than 300 mumol/l), moderate (300-600 mumol/l) or severe renal failure (greater than 600 mumol/l). Bleeding time was rarely prolonged in mild and moderate CRF and mean bleeding time significantly elevated only in severe CRF (p less than 0.005). Haematocrit was the only index which correlated with bleeding time (r = -0.40). Platelet counts, collagen stimulated thromboxane generation, and platelet aggregation responses to ADP, collagen and ristocetin were all either normal or increased in all three CRF groups, but thromboxane production in clotting blood was reduced. Plasma fibrinogen, C reactive protein and von Willebrand factor (vWF) were elevated in proportion to CRF. We found no evidence that defects in platelet aggregation or platelet interaction with vWF prolong the bleeding time in patients with progressive CRF.


Subject(s)
Bleeding Time , Blood Platelets/physiology , Kidney Failure, Chronic/blood , Platelet Function Tests , Humans , Thromboxane B2/blood
12.
J Bone Joint Surg Br ; 70(1): 127-9, 1988 Jan.
Article in English | MEDLINE | ID: mdl-3339043

ABSTRACT

The surgical correction of scoliosis in adolescents involves considerable trauma to bone and muscle which, together with hypotensive anaesthesia, might be expected to compromise renal function. Our recent observation of acute renal failure in two such patients prompted a prospective study of renal function following 52 operations in 43 patients. Despite hypotension, blood loss, muscle damage and evidence of fat embolism, renal function was unaltered in all patients, and there was no impairment of spinal cord function. Careful attention was paid to the maintenance of circulating volume which is essential to protect renal perfusion.


Subject(s)
Hypotension, Controlled/adverse effects , Kidney/physiopathology , Scoliosis/surgery , Adolescent , Adult , Child , Creatinine/metabolism , Female , Hemorrhage/etiology , Humans , Intraoperative Period , Kidney/metabolism , Male , Postoperative Complications , Prospective Studies , Scoliosis/metabolism , Sodium/metabolism
13.
Nephrol Dial Transplant ; 3(3): 257-62, 1988.
Article in English | MEDLINE | ID: mdl-3140097

ABSTRACT

Chronic renal insufficiency progresses by a final common pathway of glomerular damage characterised by microvascular injury and glomerulosclerosis. In order to investigate the possible role of blood rheology in this process, rheological indices were compared between healthy controls and a group of patients with progressive renal failure due to renal diseases that were not considered to be immunologically mediated. Plasma viscosity was significantly increased in the renal insufficiency group (P less than 0.005), and correlated with raised plasma concentrations of fibrinogen (r = 0.63; P less than 0.005). Whole-blood viscosity corrected to a standard haematocrit of 0.45 was also raised. A weak but significant correlation was seen between plasma viscosity and 24-h urinary protein excretion (r = 0.50; P less than 0.005). Our data show that in chronic renal insufficiency, rheology is abnormal. Proteinuria correlates with plasma viscosity, which is consistent with the hypothesis that raised plasma viscosity leads to an increase in glomerular capillary pressure and thence glomerular permeability. Correction of rheological abnormalities might help to preserve kidney function and reduce proteinuria in these patients.


Subject(s)
Blood Viscosity , Kidney Failure, Chronic/blood , Kidney Glomerulus , Adolescent , Adult , Aged , Erythrocyte Deformability , Female , Humans , Male , Middle Aged , Proteinuria/blood
14.
Nephron ; 43(3): 196-202, 1986.
Article in English | MEDLINE | ID: mdl-3724927

ABSTRACT

Haemodialysis patients have an exceptionally high incidence of death from cardiovascular causes, related in part to abnormalities of lipids and platelets. Eskimos, however, have a low incidence of myocardial infarction and have a high dietary intake of fish, rich in omega-3 polyunsaturated fatty acids. We have, therefore, studied the effect of a fish oil MaxEPA, containing 3.6 g of the omega-3 polyunsaturated fatty acid eicosapentaenoic acid on lipids and platelet function in haemodialysis patients. Following 8 weeks of therapy there was a 35% fall in triglycerides, a 10% rise of high-density lipoprotein (HDL) cholesterol, a 36% rise of HDL2 cholesterol fraction and a 54% rise of the HDL2:HDL3 cholesterol ratio. The platelet aggregation to adenosine diphosphate and collagen was significantly reduced. The activated whole-blood clotting time was prolonged from 141 to 153 s, and 69% of patients showed a reduction of factor VIII related antigen which is usually elevated in haemodialysis patients and is thought to be a marker of endothelial damage. The blood pressure fell from 147/82 to 124/74. We have thus shown that a dietary supplement of eicosapentaenoic acid produces potentially beneficial effects on lipids, platelets, and blood pressure and may help to protect against atheroma and thus cardiovascular mortality in high-risk haemodialysis patients.


Subject(s)
Docosahexaenoic Acids , Eicosapentaenoic Acid , Fatty Acids, Unsaturated/therapeutic use , Lipids/blood , Platelet Aggregation/drug effects , Renal Dialysis/adverse effects , Adolescent , Adult , Arteriosclerosis/etiology , Arteriosclerosis/prevention & control , Cardiovascular Diseases/etiology , Cardiovascular Diseases/prevention & control , Cholesterol/blood , Cholesterol, HDL/blood , Drug Combinations , Female , Humans , Male , Middle Aged , Triglycerides/blood
16.
Article in English | MEDLINE | ID: mdl-3887374

ABSTRACT

Dialysis with prostacyclin (Epoprostenol, PGI2) alone prevents platelet activation and endothelial cell stimulation but not the elevation of fibrinopeptide A (FPA), a sensitive marker of fibrin generation. The generation of FPA may explain why some patients develop clot in the dialysis circuit during PGI2-only dialysis. In combination with heparin, PGI2 augments the anticoagulant effect of the heparin as well as providing platelet protection.


Subject(s)
Epoprostenol/therapeutic use , Renal Dialysis/methods , Blood Platelets/drug effects , Hemorrhage/prevention & control , Heparin/therapeutic use , Humans , Thrombosis/prevention & control
17.
Br Med J (Clin Res Ed) ; 290(6461): 13-4, 1985 Jan 05.
Article in English | MEDLINE | ID: mdl-3917316

ABSTRACT

In a placebo controlled, double blind crossover study natural progesterone was given by mouth, in increasing doses, to six men and four postmenopausal women with mild to moderate hypertension who were not receiving any other antihypertensive drugs. When compared with values recorded before treatment and during administration of placebo progesterone caused a significant reduction in blood pressure, suggesting that progesterone has an antihypertensive action rather than a hypertensive one as has been previously thought. This possible protective effect of progesterone should be investigated further.


Subject(s)
Hypertension/drug therapy , Progesterone/therapeutic use , Adult , Aged , Clinical Trials as Topic , Double-Blind Method , Female , Humans , Male , Menopause , Middle Aged , Posture
19.
Thromb Res ; 36(1): 17-27, 1984 Oct 01.
Article in English | MEDLINE | ID: mdl-6506029

ABSTRACT

Impedance aggregometry allows the measurement of platelet responses in whole blood as well as in PRP. The variability of haematocrit values encountered when applying this technique to haemodialysis patients prompted an investigation of the effects of red cells on platelet aggregation in whole blood. Collagen induced aggregation was measured in both PRP and whole blood from haemodialysis patients and healthy controls. Platelets from haemodialysis patients were less aggregable than those from the controls when tested in PRP, but more aggregable when tested in whole blood. Blood samples with a range of haematocrit values were prepared by mixing PRP and autologous red cells, and used to study the effect of haematocrit on platelet aggregation. In blood from control subjects aggregation rate was reduced by rising haematocrit but no reduction of maximum aggregation occurred until haematocrit exceeded 40%. In contrast uraemic platelets showed increased responses in the presence of red cells. In a limited cross over study no significant difference was found in the effect on platelet aggregation of washed erythrocytes from uraemic and non-uraemic donors. It is concluded that red cell presence influences platelet aggregation by complex mechanisms during impedance aggregometry and that this effect must be considered when interpreting results.


Subject(s)
Erythrocytes/physiology , Platelet Aggregation , Platelet Function Tests/methods , Renal Dialysis , Uremia/blood , Chronic Disease , Collagen/pharmacology , Hematocrit , Humans , Platelet Function Tests/instrumentation , Uremia/therapy
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