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Biomedical subjects

A Davenport

Publications and source records attributed to A Davenport.

At least 19 recordsLinked to original sources
PubMed2006

Renal amyloidosis in intravenous drug users.

BACKGROUND: Intravenous drug abuse is associated with a wide variety of acute and chronic medical complications. The increased longevity of drug users has seen the emergence of new diseases as a result of chronic bacterial and viral infection. We recently observed an increase in the number of cases of renal amyloidosis among intravenous drug users in central London. AIM: To describe here the demographic and clinical characteristics of such patients. METHODS: Patients were identified retrospectively from computerized patient renal biopsy records at University College London and Royal Free Hospitals from 1990-2005. Clinical information was collected from patient hospital records. RESULTS: We identified 20 cases of AA amyloidosis; 65% occurred between January 2000 and September 2005. All were proteinuric (mean 7.3 g/l, range 0.5-14.8 g/l) and 13 required dialysis within 1 month of diagnosis. Of the remaining seven, four developed end-stage renal failure after mean follow-up of 16 months (range 6-30). Nine died, with median survival of 19 months (range 1-62); all deaths were due to sepsis. DISCUSSION: Secondary AA amyloidosis is a serious complication of chronic soft tissue infection in intravenous drug users in central London. Affected individuals invariably presented with nephrotic range proteinuria and advanced renal failure. Treatment options are limited and the outcome for such patients on renal replacement was poor. Cross-disciplinary strategies are needed to prevent this serious complication of long-term intravenous drug abuse.

Acute Kidney Injury↗
PubMed2006

Anticoagulation options for intermittent haemodialysis.

Anticoagulation of the extracorporeal circuit, once a major technical problem that delayed the development of chronic intermittent haemodialysis, is today largely taken for granted as part of normal routine practice. The initiation of coagulation in the extracorporeal hemodialysis circuit is a manifestation of bioincompatibility, due to the activation of leukocytes, platelets and the coagulation cascades, rather than simple contact of intrinsic system coagulation proteins which the dialyser surface and plastic tubing leading to activation of the contact coagulation cascade. Although unfractionated heparin remains the most commonly used anticoagulant world wide, low molecular weight heparin offers the advantage of more reliable pharmacokinetics, allowing the use of a simple single bolus, with less dialyser fouling, and perhaps more importantly, less osteoporosis, hyperkalemia and abnormal lipoprotein profile. Although regional anticoagulants are available and offer the advantage of reducing the risk of haemorrhage, these tend to be prohibitively expensive, or require increased complexity such as citrate. Unfortunately the incidence of immune mediated heparin induced thrombocytopenia appears to be increasing, and these patients require systemic anticoagulation with the direct thrombin inhibitors and/or heparinoids to prevent thrombosis.

Anticoagulants↗
PubMed2005

Relationship between hormone receptor status and tumour size, grade and comedo necrosis in ductal carcinoma in situ.

BACKGROUND: Results of the National Surgical Adjuvant Breast Project B-24 trial indicate that adjuvant tamoxifen therapy is of benefit only in oestrogen receptor (ER)- positive ductal carcinoma in situ (DCIS). In the UK, ER status is not routinely determined in DCIS. The aim of this study was to assess the ER status in women with DCIS to determine whether any clinicopathological factors could predict positivity instead of immunohistochemical assessment. METHODS: The ER and progesterone receptor (PR) status of consecutive women diagnosed with DCIS during 2001 and 2002 was determined by immunohistochemistry. RESULTS: One hundred and nineteen tumours diagnosed between 2001 and 2002 were analysed; 73.0 per cent were ER positive and 61.1 per cent were PR positive. PR positivity was associated with ER positivity (P < 0.001). Increasing tumour grade correlated with a decrease in ER and PR positivity (both P = 0.002). Comedo necrosis was associated with ER negativity (P = 0.026), PR negativity (P = 0.033) and a lower percentage of ER expression in ER-positive tumours (mean(s.d.) 82(27) versus 93(10) per cent; P = 0.021). CONCLUSION: Tumour grade and comedo necrosis were not strong enough predictors to be used as surrogates for immunohistochemical assessment. ER status should be determined before commencing endocrine therapy.

Adult↗
PubMed2005

Myeloid metaplasia in the gall bladder: a case report.

Idiopathic myelofibrosis is often associated with myeloid metaplasia (extramedullary haemopoiesis) in the spleen and liver. However, the gall bladder is an extremely unusual site for it to occur. A 59 year old man with myelofibrosis, who underwent cholecystectomy for chronic cholecystitis, showed myeloid metaplasia in his gall bladder. Pathologically, this may lead to diagnostic difficulties.

Gallbladder Diseases↗
PubMed2004

Nitric oxide production by human peritoneal mesothelial cells.

Nitric oxide (NO) has multiple actions, ranging from immunomodulation to regulation of vascular tone and capillary flow. Thus NO generation within the peritoneum could potentially affect peritoneal transport by increasing capillary vasodilatation, and regulate the response to bacterial invasion. Peritoneal mesothelial cells have a common embryological derivation with endothelial cells. As mesothelial cells are the predominant cell type lining the peritoneal cavity, they could potentially be a major source of locally produced nitric oxide. Nitric oxide was measured using the Griess reaction, as total nitrite and nitrate, in fresh unused and spent dialysate effluent (SPDE) from both healthy peritoneal dialysis patients, and during episodes of bacterial peritonitis. Whereas fresh CAPD dialysate was nitrite free (5 +/- 0.1 microM), SPDE from a standard 4 h day time exchange contained 10.2 +/- 0.6 microM/L/h, and that from the overnight dwell 9.1 +/- 0.7 microM/L/h. During an episode of peritonitis, dialysate nitrite and nitrate increased significantly from 9.0 +/- 1.0 microM/L/h, when not infected to 17.5 +/- 2.4, from the first CAPD bag drained at presentation, and 15.2 +/- 1.8 for the second and 16.0 +/- 2.5 for the third exchange (p<0.01). By the following day nitrite levels had returned to baseline, 7.0 +/- 1.0 microM/L/h. Human peritoneal mesothelial cells (HPMC) were cultured and found to produce nitric oxide (261 nmol/mg cell protein), which increased in a dose dependent manner with the addition of spent uninfected CAPD dialysate. The addition of L-arginine, a NO substrate resulted in a 10% increase in nitric oxide production, whereas the addition of the blocker L-NMMA produced a 10% reduction. RNA for inducible nitric oxide synthase (iNOS) was sought using northern blotting technique following combination stimulation with lipopolysaccharide and cytokines (IL-1beta, TNFalpha and gamma-INF, and/or spent dialysate from patients with bacterial peritonitis). However, we could not demonstrate RNA production for iNOS. Peritoneal mesothelial cells may be an important source of locally generated nitric oxide within the peritoneal cavity under basal conditions, but as they do not contain iNOS, the markedly increased NO production observed with episodes of acute bacterial peritonitis is more likely due to a combination of increased NO production by peritoneal macrophages and endothelial cells.

Adolescent↗
PubMed2003

Scleromyxoedema-like changes in four renal dialysis patients.

We describe four renal dialysis patients from our hospital who, over a 6-month period, developed erythematous, thickened, indurated dermal plaques. The plaques were limited to the limbs and in three patients there were associated flexion contractures. The clinical features most resembled scleromyxoedema. All patients had previously received at least one renal transplant. Histopathology of the plaques showed features of scleromyxoedema in two patients, whereas the other two showed a different picture, more suggestive of a morphoea-like process. There are important differences between our patients and classical scleromyxoedema. All four patients had normal immunoglobulins and no paraprotein was detected. Almost all cases of classical scleromyxoedema are associated with an IgGlambda paraproteinaemia. We have not yet identified an underlying cause for this cluster of cases in our hospital. It is possible that the skin changes seen may have been precipitated by an environmental agent, such as in 'toxic oil syndrome' and vinyl chloride-induced scleroderma. We discuss the differences between our patients and those with scleromyxoedema, localized or generalized morphoea and environmentally induced scleroderma. We feel that our patients show a constellation of features similar, but not identical, to scleromyxoedema. There has been only one previous report of similar patients. We believe this to be a new and distinct phenomenon.

Adult↗
PubMed2003

Expression of Ki-67 and cytokeratin 20 in hyperplastic polyps of the colorectum.

AIMS: To study the expression of Ki-67 and cytokeratin 20 (CK20) in a group of hyperplastic polyps (including a group with "atypical" features) with the aim of determining whether upper crypt Ki-67 staining and lower crypt CK20 staining correlated with these atypical features, as assessed by light microscopy. METHODS: Fifty seven formalin fixed, paraffin wax embedded hyperplastic colorectal polyps from 53 patients were selected on histological grounds; these comprised 26 typical polyps and 31 with atypical features, which included nuclear hyperchromatism, basal crowding, and increased mitotic activity. These polyps were examined using a standard immunohistochemical method with antibodies against CK20 and Ki-67. Comparisons were made with normal mucosa, adenomatous polyps, and carcinomas. RESULTS: Of the 26 typical polyps, 17 showed the usual pattern of lower crypt Ki-67 and upper crypt CK20 staining; one with upper crypt Ki-67 staining but normal surface CK20 staining; seven with Ki-67 confined to the lower half of crypts but with scattered lower crypt CK20; and one with both upper crypt Ki-67 staining, together with scattered CK20 basal staining. Of the 31 polyps with atypical features, 11 showed the usual staining pattern of lower crypt Ki-67 staining and surface staining with CK20; two showed Ki-67 staining extending into the upper half of crypts, but with a normal surface staining with CK20; 14 showed Ki-67 confined to the lower half of crypts, but scattered lower crypt staining with CK20; and four showed upper crypt Ki-67 staining together with scattered CK20 lower crypt staining. CONCLUSIONS: The normal pattern of lower crypt Ki-67 and upper crypt CK20 was seen in 28 of the 57 hyperplastic polyps and, in general, this corresponded with standard light microscopic appearances. Twenty one of the 57 polyps showed lower crypt mosaic CK20 staining, which in general corresponded with basal abnormalities on light microscopy, although seven specimens had normal appearances. Two smaller subsets emerged, one showing upper crypt Ki-67 staining in the presence of normal CK20 expression (three cases) and another in which a combination of lower crypt CK20 and upper crypt Ki-67 expression was seen (five cases). This last pattern was similar to that of neoplastic polyps and raises the possibility that a subgroup of hyperplastic polyps exists that may be a variant with malignant potential. Further studies with markers of mismatch repair genes and K-ras mutations may help to clarify this issue.

Adenomatous Polyps↗
PubMed2003

Life before birth: effects of cortisol on future cardiovascular and metabolic function.

UNLABELLED: The concept of fetal programming is an area that is now under rigorous investigation in many laboratories throughout the world. We need to engender a fascination in all segments of society, not just pregnant women, about life in the womb. CONCLUSION: Everyone needs to understand that improving the condition of the fetus will have personal, social and economic benefits. The time has come to realize that, in a sense, it is not just women who are pregnant but it is the family and the whole of society.

Animals↗
PubMed2001

The outcome of ambulatory DVT management using a multidisciplinary approach.

Low molecular weight heparins (LMWHs) have been demonstrated to be at least as safe and effective as unfractionated heparin (UFH) in the initial management of deep vein thrombosis (DVT). However, the effectiveness of using LMWH in the ambulatory management of DVT in a 'real-life' setting has yet to be evaluated. This multicentre retrospective study involving 697 patients considers the outcome data of patients under- going ambulatory DVT treatment with tinzaparin (Innohep(R), Leo Pharmaceuticals, Risborough, Buckinghamshire, UK). During the 6 months following presentation, 17 (2.5%) patients had confirmed thromboembolic complications, of which 14 occurred subsequent to the initial LMWH treatment phase ('late'). There were no deaths in this group. Bleeding complications were reported in 23 (3.4%) patients, with 13 of these being classified as 'late'. Of these, two events were considered major resulting in hospitalization and death. Hospitalization for all causes was 6.8% (45 patients) with 32 patients being admitted for thromboembolic or bleeding complications. Overall mortality was 6.7%. These results compare favourably with published clinical trial data. This study demonstrates that ambulatory treatment of proven DVT with LMWH is both safe and effective.

Adolescent↗
PubMed2001

Atrial thrombus and central venous dialysis catheters.

A native arteriovenous fistula is the first choice for hemodialysis access. Despite improved catheter designs and the use of internal jugular veins, thrombotic complications still occur when tunneled central venous catheters are used as an alternative. Although right atrial thrombus (RAT) is a well-characterized complication of long-term central venous cannulation, particularly when used for parenteral nutrition and chemotherapy in pediatric practice, only 9 reported cases previously have been associated with the long-term use of central venous catheters for hemodialysis. We report five cases of RAT seen at our unit between 1994 and 1998 in patients who had been dialyzed using tunneled catheters. In four of five cases, the diagnosis was made during the investigation of hemoptysis or dyspnea. In the fifth case, a screening transthoracic echocardiogram revealed the thrombus. Three of five of the patients suffered pulmonary emboli, and a fourth patient had an unexplained electromechanical dissociation cardiac arrest without definite evidence of pulmonary embolus. Our experience suggests that anticoagulated patients with RAT remain at risk of pulmonary embolism. One of our patients successfully underwent atrial thrombectomy. In four of five of our cases and four of nine cases in the literature, the central venous catheter tip was within the right atrium. Positioning of the central venous catheter tip low down in the superior vena cava or in the right atrium has been advocated to improve dialysis adequacy and to reduce the incidence of catheter thrombosis. However, placement of the catheter tip within the right atrium may be associated with an increased risk of RAT.

Adolescent↗
PubMed2001

Ultrafiltration in diuretic-resistant volume overload in nephrotic syndrome and patients with ascites due to chronic liver disease.

Patients with nephrotic syndrome and those with cirrhosis are predisposed to salt and water retention due to reduced renal sodium excretion. Despite the prescription of low-sodium diets and diuretics, some patients develop refractory oedema. When other medical treatments have been ineffective, isolated ultrafiltration and hemofiltration have been successfully used to treat refractory nephrotic patients. Following fluid removal, patients become responsive to diuretics. In cirrhotic patients, re-infusion of ascites and paracentesis with albumin infusion have been reported to be equally effective in managing ascites refractory to diuretic and other standard therapies. Although isolated ultrafiltration has not been successful in controlling ascitic fluid, hemofiltration has been shown to be beneficial, whereas standard intermittent hemodialysis has been reported to be ineffective.

Ascites↗
PubMed2001

The safety and efficacy of MMF in lupus nephritis: a pilot study.

Inducing and maintaining remission in patients with lupus nephritis may be difficult. Current treatments have significant toxicity. Mycophenolate mofetil (MMF) limits damage in murine models of lupus nephritis. We have assessed the efficacy and tolerability of MMF in the treatment of patients with long-standing or resistant lupus nephritis. We have treated 13 patients with biopsy proven lupus nephritis (two membranous nephropathy, four membranous nephropathy with superimposed proliferative changes, seven with proliferative glomerulonephritis). All patients had relapsed on conventional treatment or there were pressing indications to minimise steroid dosage or avoid alkylating agents. Nine out of 13 were treated with MMF and prednisolone, 3/10 with MMF alone and 1/10 with MMF, prednisolone and cyclosporine. Thirteen patients were treated with MMF for up to 37 months (median 25 months). Three patients were withdrawn from MMF during the first 8 months of treatment. The remainder tolerated MMF (median dose 1 g/day). Serological improvements were observed in 9/13 and steroid dosage was reduced in 8/10 patients. Infections occurred in 3/13. One patient relapsed. MMF significantly reduced the rate of decline of renal function. MMF should be considered in the treatment of long-standing or resistant lupus nephritis. Controlled clinical trials are required to confirm these findings.

Adrenal Cortex Hormones↗
PubMed2001

Renal replacement therapy in the patient with acute brain injury.

The patient with an acute brain injury requiring renal replacement therapy presents a major problem in that conventional intermittent hemodialysis may exacerbate the injury by compromising cerebral perfusion pressure, either after a reduction in cerebral perfusion or because of increased cerebral edema. Compared with standard intermittent hemodialysis, the continuous forms of renal replacement therapy (CRRT) provide an effective therapy in terms of solute clearance, coupled with improved cardiovascular and intracranial stability. The disadvantage of CRRT is that anticoagulation may be required, and anticoagulants with systemic effects may provoke intracerebral hemorrhage, either at the site of damage or around the intracranial pressure monitoring device. Although peritoneal dialysis does not require anticoagulation, the clearances achieved are often less than those of CRRT, and sudden changes in intraperitoneal volume may provoke cardiovascular and thus intracranial instability.

Acute Kidney Injury↗
PubMed2001

Dialysate and substitution fluids for patients treated by continuous forms of renal replacement therapy.

The development of CRRT from simple arteriovenous ultrafiltration with a treatment using 50 liters a day, has necessitated the development of specialized dialysate/replacement solutions. As the volumes used are large, quality control is vitally important not only in terms of electrolyte composition, but also preventing bacterial and endotoxin contamination. Lactate remains the standard anionic base, as this increases fluid storage time and reduces the risk of bacterial contamination. Some centers use citrate anticoagulation, and the citrate load provides an adequate supply of anionic base to control metabolic acidosis. However, patients receiving very high volume exchanges, or those with severe tissue acidosis and/or liver failure, may be unable to convert the lactate, or citrate load effectively, resulting in hyperlactatemia or hypercitratemia and acidosis. In these circumstances, bicarbonate-based fluids are advantageous. The use of bicarbonate-based dialysate/replacement fluid during CRRT does not mask lactate overproduction, and lactate remains a reliable marker of tissue oxygenation in patients treated by CRRT. Bicarbonate CRRT alone does not treat metabolic acidosis, but allows better control of acidosis, thereby allowing time for the institution of other therapies designed to reverse the underlying cause.

Acid-Base Equilibrium↗
PubMed2000

Effects of lactate-buffered and lactate-free dialysate in CAVHD patients with and without liver dysfunction.

BACKGROUND: Continuous modalities of renal replacement deplete patients of bicarbonate, which is traditionally replaced indirectly by lactate in dialysate or replacement fluids. We have compared a new lactate-free dialysate (unbuffered dialysate with separate bicarbonate replacement of dialytic bicarbonate loss) with standard lactate-buffered dialysate in terms of acid-base control, lactate accumulation, and hemodynamic stability in patients undergoing continuous renal replacement therapy in an intensive care unit. METHODS: A nonrandomized crossover cohort study involving 54 patients with multi-organ failure (of whom 19 had significant hepatic dysfunction) was performed. All patients completed 24-hour continuous hemodiafiltration against both lactate-buffered and lactate-free dialysate. Arterial pH, blood gases, bicarbonate, and lactate, venous sodium, blood pressure, and inotrope requirements were measured before and at six hourly intervals during the first 24 hours of dialysis against each dialysate. RESULTS: Lactate-free dialysate provided more rapid control of acidosis than lactate buffered with less total administration of buffer than that given during the lactate-buffered period (total mmol bicarbonate vs. total mmol lactate + bicarbonate). Lactate accumulation was slight in both periods, but was higher during lactate-buffered continuous venovenous hemodiafiltration (CVVHD). The mean arterial pressure rose during lactate-free dialysis with decreased inotrope doses and fell during lactate-buffered dialysis with increased inotrope requirement. Results in patients with liver dysfunction were not significantly different from those without it. CONCLUSIONS: Over the time scale of 24 hours, lactate derived from continuous dialysis circuits is efficiently cleared from the blood of most patients with multi-organ failure, but with less effect on systemic acidosis than is produced by equivalent amounts of bicarbonate.

APACHE↗