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Biomedical subjects

D J Goldsmith

Publications and source records attributed to D J Goldsmith.

At least 19 recordsLinked to original sources
PubMed2006

Anaemia in diabetic patients with chronic kidney disease--prevalence and predictors.

AIMS/HYPOTHESIS: We investigated the relationship between haemoglobin (Hb) and diabetes in patients with renal disease. SUBJECTS, MATERIALS AND METHODS: All adult patients with stable chronic kidney disease attending renal or diabetic outpatient clinics in a six-month period were identified. Patients' notes and electronic patient records were used to build a comprehensive biochemical and clinical database. Results were analysed for the predictors of Hb, the severity of anaemia in both groups and the relative impact of diabetes on haemoglobin and anaemia. RESULTS: The study group consisted of 468 patients, of whom 204 had diabetes and 264 did not. At every level of renal function haemoglobin levels were lower by an average of 10 g/l in subjects with diabetes than in those without. Likewise, anaemia was found to occur at an earlier stage of chronic kidney disease (and to be of greater severity) in diabetic patients. Independent predictors of haemoglobin included female sex, diabetes, renal function and serum albumin, with diabetes and renal function being the greatest predictors. Multiple logistic regression showed that patients with diabetes had an odds ratio of 4 for being anaemic. Had we used an estimated GFR of less than 60 ml/min to trigger investigation of anaemia, we would have detected 85% of anaemic patients. CONCLUSIONS/INTERPRETATION: Anaemia is frequently found in diabetic patients with renal disease, occurs earlier and is more severe than in similar but non-diabetic subjects. In contrast to previous publications, our findings suggest that anaemia is prevalent at the earliest stages of chronic kidney disease. We advocate an estimated GFR threshold of <60 ml/min to trigger investigation for anaemia in diabetic subjects.

Adult↗
PubMed2006

Familial juvenile hyperuricaemic nephropathy is not such a rare genetic metabolic purine disease in Britain.

Renal disease is rare today in classic adult gout, and gout is rare in renal disease--especially in the young. Here we summarise studies in 158 patients from 31 kindreds diagnosed with familial juvenile hyperuricaemic nephropathy FJHN from a total of 230 kindred members studied in Great Britain. Some patients have been followed for up to 30 years, and allopurinol has ameliorated the progression of the renal disease in all 113 surviving members provided: They have been diagnosed and treated sufficiently early. Compliance with allopurinol treatment and diet has been as important as early recognition. Hypertension has been rigorously controlled. The use of oral contraceptives has been avoided, as has pregnancy in any female with a Glomelar Filtration Rate GFR <70 ml/min. The question arising is: Why is FJHN the most prevalent genetic purine disorder diagnosed in Britain? Is it a lack of awareness which needs to be improved Europe-wide?

Adolescent↗
PubMed2005

Antiangiogenic agents: studies on fumagillin and curcumin analogs.

Cancer is a general term used to describe many disease states, each of which are characterized by abnormal cell proliferation. The causes which bring about this abnormal cellular behavior are specific to each type of cancer. The success of tumor-targeted therapy is limited by this diversity. One common denominator for all types of cancer is the requirement of a suitable blood supply. Therefore, tumor vasculature has emerged as a potential target for therapeutic intervention. New blood vessel growth from preexisting vasculature stimulated by biochemical signals is termed angiogenesis. Tumor masses require a constant supply of oxygen and nutrients, and a means of efficient waste removal to ensure sustained development. Diffusion from nearby capillaries can supply adequate nutrition for tumors less than 2 mm in size, but for continued growth the tumors must develop their own blood supply. Alteration of the delicate balance of angiogenic stimulating factors and angiogenic inhibitors results in the phenotypic change from quiescence to active endothelial proliferation. To date, this angiogenic switch is not completely understood. The goal of antiangiogenic therapy is to interfere with these mechanisms and prevent tumor cells from developing a viable blood supply. Fumagillin is a naturally occurring antifungal agent. Curcumin is a natural product isolated from the spice turmeric. Both compounds have been shown to have antiangiogenic properties in vitro and in vivo. This paper describes efforts to design and prepare fumagillin and curcumin analogs and evaluate their corresponding antiangiogenic activities.

Angiogenesis Inhibitors↗
PubMed2001

Coronary artery disease in uremia: Etiology, diagnosis, and therapy.

Cardiovascular disease is a major challenge to nephrologists, whether we deal with patients with pre-end-stage renal failure, on dialysis or after successful renal transplantation. It is the most common cause for death in patients with a functional allograft, and prevents many dialysis patients from being engrafted. Coronary artery disease is a diagnostic and therapeutic challenge, as it differs in some respects from that seen in non-uremic cohorts, and lacks much of the evidence-base on which therapeutic intervention rests. This review examines the experimental and clinical literature on cardiovascular disease in uremia, focusing on coronary artery disease. We focus on the incidence, presenting syndromes, screening tools, and interventions in the context of acute and chronic coronary syndromes. Recent evidence comparing coronary angioplasty, coronary artery stenting, and bypass surgery in subjects with renal failure is also reviewed. Coronary artery disease is more prevalent in uremia, more difficult to diagnose and less rewarding to treat compared to non-uremic subjects. Many more randomized trials are needed. In the absence of information from such trials, we advocate aggressive control of conventional and novel cardiovascular risk factors, and early intervention for symptomatic coronary disease.

Arteriosclerosis↗
PubMed2001

Spontaneous abdominal hemorrhage with AA-amyloidosis and vasculitis in a patient with rheumatoid arthritis.

Both rheumatoid vasculitis and amyloidosis in rheumatoid arthritis (RA) are uncommon. We describe a patient in whom they occurred together and were associated with fatal intra-abdominal hemorrhage. A 56-year-old Caucasian woman was referred because of increasing lethargy, edema, and proteinuria. She had suffered from seropositive, erosive, nodular RA for 14 years. Previously, she had undergone numerous joint replacements, a thyroidectomy for amyloid-associated (AA) amyloidosis of the thyroid that caused a large goiter and a renal biopsy that showed renal AA-amyloidosis in the context of nephrotic syndrome. As her condition deteriorated, this patient became increasingly reluctant to go to the hospital and to take drugs beyond analgesics. Thus, her RA was chronically under treated. While in the hospital for evaluation, this patient suddenly developed hypotension, tachycardia, and a severe colicky left-sided abdominal pain radiating from the left upper quadrant/epigastric region to the left iliac fossa. Computed tomography (CT) showed a large amount of echogenic free fluid within the abdomen and marked thickening of the omentum. At laparotomy, 2 liters of free blood was found adjacent to a hematoma of the greater omentum, and it was evacuated without identification of a discrete bleeding point. All solid and hollow organs were normal. The omentum was noted to be very friable. She developed a more disseminated bleeding diathesis and persistent peritoneal hemorrhage via her abdominal drains. She succumbed shortly afterward. Histology revealed extensive omental hemorrhage and one large vessel within the area of hemorrhage showed a severe necrotizing vasculitis. Extensive amyloid deposition was also found within the walls of the smaller omental arterioles. Vasculitis in the context of RA is relatively rare and is associated with under treated, seropositive disease. Skin and nerve involvement are most common, but bowel involvement has been reported, with a highly significant morbidity (partly due to late presentation/recognition). Similarly, AA-amyloidosis is a rare but feared long-term concomitant of under treated RA. Early recognition can permit successful anti-inflammatory therapy to affect a clinical and pathological remission; continued inflammatory stimulation is associated with rapid progression and demise. Chronically under treated patients with RA are more prone to rare but potentially devastating complications. Gastrointestinal catastrophes are a feature of both rheumatoid vasculitis and of amyloidosis, here uniquely co-localized.

Journal Article↗
PubMed2001

Nephrotic syndrome and mesenteric infarction secondary to metastatic mesothelioma.

Malignant mesothelioma can present insidiously with progressive breathlessness and chest pain. Paraneoplastic, or non-chest related, presentations are very rare. The case of an elderly man with occupational exposure to asbestos who presented with nephrotic syndrome due to minimal change nephropathy in the context of advanced pleural mesothelial malignancy is reported.

Aged↗
PubMed2001

Coronary artery disease in patients with renal failure.

Cardiovascular disease is prevalent in patients with advanced renal failure or on dialysis treatment, and after renal transplantation. The risk factors for the cardiovascular problems are a mixture of conventional and novel ones. Inflammation and oxidation may be especially important in the acceleration of atherosclerosis in chronic renal failure. This article discusses these factors and gathers together the evidence for cardiovascular intervention and treatment in a group of patients whose overall mortality is high.

Acute Kidney Injury↗
PubMed2000

Reduced blood pressure diurnal variability as a risk factor for progressive left ventricular dilatation in hemodialysis patients.

Cardiovascular mortality places a considerable burden on chronic renal replacement therapy programs. Left ventricular hypertrophy (LVH) increases the risk for cardiovascular mortality. Risk factors for LVH in the dialysis population are numerous and include arterial distensibility, hypertension, anemia, arteriovenous fistula, and hyperparathyroidism. An important factor to consider in the diagnosis and evaluation of hypertension in this clinical setting is blood pressure (BP) level variation, only accessible using ambulatory BP monitoring (ABPM). In uremic patients, a relative elevation of BP during sleep periods leading to an increased 24-hour BP load is frequently described. Whether this additional BP burden is pathophysiologically significant has not been resolved. This study is designed to examine the effect on echocardiographically derived measurements of the left ventricle in 60 stable chronic hemodialysis patients of abnormal (reduced) diurnal BP variability, measuring ambulatory BP on three occasions and performing echocardiography twice over a 12-month period. First, we found that most dialysis patients (76%) had consistent diurnal BP rhythms over a 12-month period, and second, those patients with persistently reduced diurnal BP rhythm tended to develop a dilated left ventricle and left atrium in the absence of other known and/or relevant risk factors (persistently increased sleep BP group; n = 36; LV end-diastolic diameter, 38.2 +/- 2.5 mm/m(2) versus persistently normal sleep BP group; n = 10; LV end-diastolic diameter, 30.6 +/- 3. 3 mm/m(2); P < 0.05). These results suggest that persistent abnormal BP variability is a risk factor for a dilated heart on dialysis, independent of the BP level.

Adult↗
PubMed2000

Analysis of the effect of hemodialysis on peripheral and central arterial pressure waveforms.

BACKGROUND: Arterial stiffening is very pronounced in renal patients. Carotid artery stiffening is a powerful predictor of future cardiovascular mortality, and measures of arterial compliance correlate much better with left ventricular mass (LVM) in dialysis patients than does brachial artery blood pressure (BP). The aim of our study was to describe the influence of a hemodialysis (HD) session on arterial cushioning function and to correlate the potential different types of behavior with echocardiographic derived parameters. METHODS: Radial artery pressure waveforms were measured and recorded noninvasively by applanation tonometry in 51 healthy patients on regular three times weekly HD. The data were then converted into aortic pressure waveforms using a regression equation (SphymoCortrade mark apparatus). Measurements were done pre- and post-HD in order to ascertain the effect of a single HD session on arterial hemodynamics. The augmentation index (AGI; the difference between early and late pressure peaks divided by the pulse pressure amplitude) was used as an index for vascular compliance. Reproducibility was assessed in 20 young healthy subjects by determining the aortic pulse wave augmentation index twice from radial artery BP measurements one minute apart. Intraobserver error was 2.4%. For 10 dialysis patients similarly studied, the intraobserver error was 1.6%. RESULTS: AGI was correlated with subjects' height (r = -0.37, P = 0.009), weight (r = -0.41, P = 0.002), and BP levels: radial systolic BP (r = 0.33, P = 0.018), radial diastolic BP (r = 0.29, P = 0.036), and central systolic BP (r = 0.51, P < 0.001). Comparing the pre- with the post-HD AGI values, four patterns of evolution became apparent: (1) The AGI was negative before the HD session and became even more negative afterward (N = 3 out of 51). (2) The AGI was positive before the HD session but became negative after dialysis (N = 19 out of 51). (3) The AGI was positive before the HD session and, although diminished afterward, remained positive (N = 23 out of 51). (4) The AGI was positive before the HD session and increased afterward (N = 6 out of 51). We also found that in some patients, AGI remained at lower than predialysis levels for at least 24 hours. Significant relationships between echocardiographic parameters and pulse wave contour (PWC) variables included pre-HD AGI and LVM (r = 0.47, P < 0. 001). There was better correlation between LVM and derived predialysis aortic systolic BP (r = 0.56, P < 0.001) than measured brachial (peripheral) systolic BP (r = 0.35, P = 0.04). Patients whose waveform remained abnormal (AGI remained positive) after HD had a more dilated LV (LV-EDD = 52.07 +/- 3.48 mm) than did those patients for whom HD restored "normal" arterial hemodynamics (LV-EDD 46.86 +/- 4.06 mm, P < 0.05). CONCLUSIONS: A standard HD session profoundly affected aortic BP waveform characteristics, with a reduction in wave reflection in 88% of patients. However, restoration by HD of a normal aortic waveform was unusual. Patients whose waveform remained abnormal after HD had larger more dilated LV chambers than did those patients for whom HD restored "normal" arterial hemodynamics.

Adult↗
PubMed2000

Renal arterial intervention and angiotensin blockade in atherosclerotic nephropathy.

Atherosclerotic renal arterial disease (ARAD) is becoming a more important cause of end-stage renal failure. Diagnosis is more easily achieved because of greater clinical suspicion and more refined screening tools. However, the medical and interventional management of patients with ARAD is not well defined in the literature because there have been few randomized trials. Because the use of angiotensin-converting enzymes (ACE) inhibitors, and more recently angiotensin-antagonists, has become much more widespread, it is inevitable that we should, knowingly or not, give these drugs to patients with ARAD. We describe 2 case studies in which the angiotensin-antagonist irbesartan was given to 2 patients with effectively single-functional kidneys after successful renal arterial radiologic intervention. The rationale for the use of irbesartan was to control BP, which had not responded to the initial arterial intervention, and took place in patients both refractory to, and intolerant of, many other anti-hypertensive drugs. Irbesartan successfully and safely reduced systemic BP, measured by use of ambulatory BP, without prejudicing renal function (measured by use of individual kidney function GFR).

Aged↗
PubMed2000

Parathyroid carcinoma in a dialysis patient.

A 75-year-old woman who had been receiving dialysis for 3 years and had a long history of chronic renal failure attributable to reflux nephropathy was investigated for progressive hypercalcemia in the context of very high intact parathormone (iPTH) levels. Imaging showed two functional parathyroid glands in the neck. At parathyroidectomy, four variously enlarged parathyroid glands were found and completely resected, without autotransplantation. The histology of one of the glands showed invasive parathyroid carcinoma. Parathyroid carcinoma is a very rare condition, with only 16 previous cases involving dialysis patients described in the literature. We review the literature to draw together presentational and therapeutic information on the management of this problem in the setting of renal replacement therapy.

Aged↗
PubMed2000

Facet joint osteomyelitis in a patient on long-term hemodialysis.

Spinal osteomyelitis is a recognized complication in dialysis patients related to hematogenous spread of infection during bacteremia-septicemia. These episodes are often associated with sepsis due to temporary dialysis access. We describe the case of an unfortunate man whose osteomyelitis was located in the posterior facet joints. Such infection is rare and in the reviewed literature is usually associated with a more favorable outcome than described here.

Adult↗
PubMed2000

Successful medical treatment of acute bilateral emphysematous pyelonephritis.

Emphysematous pyelonephritis most often presents as an acute medical emergency, typically in a septic diabetic patient with acute renal failure. The management of this condition has traditionally been surgical, with nephrectomy. However, some recent reports have described successful medical interventions. We describe a case of acute bilateral emphysematous pyelonephritis in a frail patient not suitable for bilateral nephrectomy and long-term dialysis. This condition was managed medically, not surgically, with intensive antibiotic and circulatory support. The outcome was complete recovery after months of hospital-based treatment. We discuss the management of this rare but important condition in detail.

Acute Kidney Injury↗