Biomedical subjects
J Walshe
Publications and source records attributed to J Walshe.
Implications of colonization of vancomycin-resistant enterococci (VRE) in renal dialysis patients. Learning to live with it?
Vancomycin-resistant enterococci (VRE) commonly colonize, but less frequently infect, debilitated patients, such as those on chronic renal dialysis. The emergence of VRE amongst our cohort of renal replacement therapy patients posed considerable challenges in our attempts to prevent spread. Although 60 of 451 (13%) patients became colonized, only two patients required systemic antibiotics for confirmed or suspected invasive infection. Mortality and inpatient stay was greater in VRE-positive compared with VRE-negative patients (50% versus 10%) and patients who were screened on three or more occasions were likely to remain positive (e.g. 56% of patients screened on six occasions were positive). The application of recommended guidelines for the control of VRE, however, severely disrupted our renal dialysis programme and therefore had to be abandoned. As patients on renal dialysis are more likely to acquire VRE, remain colonized, require antibiotics and require regular inpatient or outpatient care more frequently than other patients, control measures should be adapted to minimize spread but not disrupt important and essential medical services.
Expression of FGFR1, FGFR2 and FGFR3 during early neural development in the chick embryo.
Studies involving chick embryos have implicated FGFs in neural induction and patterning as well as in other developmental events. Detailed analyses of FGF receptor expression at early stages of neural development have not been reported for the chick embryo and are incomplete for other vertebrate classes. Here we show the expression patterns of three FGF receptors, (FGFR1, FGFR2 and FGFR3) in embryonic stages between gastrulation and limb bud formation, focussing particularly on neural tissues. Between neural induction and neurulation, all three receptors are expressed in the neural plate albeit with distinct and overlapping distributions. During early neuromere formation FGFR1 transcripts are present throughout the neural tube, while transcripts for FGFR2 and FGFR3 become restricted to regions of the diencephalon and spinal cord. A little later, FGFR2 and FGFR3 are additionally expressed in the anterior midbrain and within the hindbrain. During later neuromere development, FGFR1 transcripts become localised to the telencephalon, anterior dorsal diencephalon and throughout the midbrain and hindbrain, whereas FGFR2 mRNA is restricted to dorsal telencephalon, dorsoanterior midbrain and hindbrain. FGFR3 is also expressed in anterior midbrain and hindbrain during this developmental period, and is additionally expressed in the posterior telencephalon, in the pretectum, and at the zona limitans intrathalamica. The observed expression patterns of all three receptors within the hindbrain, including rhombomere boundaries, are complex and dynamic. Expression patterns within the somites, eye, head mesenchyme, branchial arches, limb buds, nephric kidney and pharynx are also described.
Regulation and function of FGF8 in patterning of midbrain and anterior hindbrain.
In this article, an adjunct to a platform presentation at the Winternational 2000 Symposium, we summarize the recent findings of this group concerning the regulation and functions of FGF8 expressed at the isthmus of the developing brain. We show that several different FGF8 isoforms, ectopically expressed in midbrain or posterior forebrain, are able to mimic the proliferative and patterning functions previously attributed to the isthmus in tissue grafting studies. Moreover, we also show that FGF8 protein is sufficient to induce an ectopic isthmic organiser (Fgf-8+, Gbx2+) in anterior midbrain. We also provide evidence that isthmic FGF8 patterns anterior hindbrain, repressing Hox-a2 expression and setting aside a territory of the brain that includes the cerebellar anlage. We show that these effects of FGF8 are likely to be mediated via FGFR1 and be modulated by the putative FGF antagonist, Sprouty2, identified using a differential display screen. Finally, we provide evidence that the onset of Fgf8 expression is regulated by En1 and that its expression at the isthmus is subsequently maintained by a specific and direct interaction between rhombomere 1 and midbrain.
Comparison of digital subtraction angiography with gadolinium-enhanced magnetic resonance angiography in the diagnosis of renal artery stenosis.
Renal artery stenosis (RAS) is a treatable cause of hypertension and renal failure for which no ideal screening technique is currently available. We evaluated the use of dynamic gadolinium-enhanced magnetic resonance angiography (MRA) for the diagnosis of RAS. Sixty-two patients with secondary hypertension were enrolled in the study. All patients had conventional renal angiography and gadolinium enhanced MRA. The sequence used was a 3D FMP SPGR sequence with the following parameters (TR: 26 ms, TE: 6.9 ms, flip angle 40 degrees, field of view 36 x 36 cm, matrix 246 x 256, 1 excitation). Gadolinium 0.3 mmol/kg was administered and 60 1. 5-mm-thick partitions were obtained over a duration of 3.5 min. The MRA images were then compared with conventional digital subtraction angiography (DSA) images. Conventional DSA demonstrated 138 renal arteries, whereas gadolinium-enhanced MRA demonstrated 129 (93 %). Twenty-one renal artery stenoses and four occluded arteries were seen at conventional DSA. Gadolinium-enhanced MRA had a sensitivity of 88 %, specificity of 98 %, accuracy of 96 %, positive predictive value of 92 % and negative predictive value of 97 % when compared with conventional DSA. Gadolinium-enhanced MRA is an accurate technique for identifying patients with RAS. It is less sensitive in picking up accessory renal arteries.
Evaluation of dynamic gadolinium-enhanced breath-hold MR angiography in the diagnosis of renal artery stenosis.
OBJECTIVE: The aim of our study was to evaluate a three-dimensional gadolinium-enhanced breath-hold MR angiography sequence using standard MR gradients in detecting renal artery stenosis. SUBJECTS AND METHODS: Forty-two patients referred for angiography for suspected renal artery stenosis underwent both conventional digital subtraction angiography (DSA) and MR angiography. MR angiography was performed on a 1.5-T scanner with standard gradients. A fast multiplanar spoiled gradient-echo sequence was used with the following parameters: TR/TE, 10.3/1.9; flip angle, 45 degrees; field of view, 36 x 32 cm; matrix size, 256 x 128; one excitation; volume thickness, 70 mm; and partitions, 28. Gadolinium was administered IV as a dynamic bolus of 30-40 ml. Conventional and MR angiographic images were interpreted by two radiologists in consensus. RESULTS: DSA revealed 87 renal arteries, of which 79 were in 35 patients with native kidneys and eight arteries were in seven patients with transplanted kidneys. Gadolinium-enhanced MR angiography showed 85 (98%) of 87 renal arteries. Seventeen patients had 20 significant (>50% stenosis) renal artery stenoses and five patients had five occluded renal arteries revealed by DSA. MR angiography revealed 85 renal arteries (98%), 20 stenoses (100%), and five occlusions (100%). Gadolinium-enhanced MR angiography led to one false-positive interpretation for renal artery stenosis and no false-negative interpretations. Thus, the sensitivity, specificity, and accuracy of MR angiography for renal artery stenosis were 100%, 98%, and 99%, respectively. CONCLUSION: The MR angiography pulse sequence we used was an effective and reliable technique for the diagnosis of renal artery stenosis. The sequence can be performed on widely available MR equipment that does not require fast gradient hardware.
Clostridium difficile colitis associated with chronic renal failure.
BACKGROUND: Clostridium difficile-associated diarrhoea (CDAD) is a potentially life-threatening illness which has been shown to be more common and more severe in patients with chronic renal failure (CRF) than in other groups. A review of CDAD in our nephrology unit was carried out. METHODS: A review of microbiology and histology records identified 32 cases of CDAD in the nephrology unit over a 24-month period. Patient notes were reviewed to identify risk factors, clinical features and outcome. Available isolates of C. difficile underwent 16S ribosomal RNA typing. RESULTS: The incidence of CDAD in the nephrology unit was 10.7 per 1000 admissions, compared to 2.7 per 1000 in other areas of the hospital (P<0.0001). CDAD was considered the sole or principal cause of death in six (19%) and was considered a contributing factor in a further seven (22%). Mortality was significantly higher among patients with established CRF (P=0.04). Seven cases occurred as a cluster, over a 1-month period. Isolates from this cluster, along with comparative strains from other areas of the hospital, were found to be PCR type 1. Diarrhoea occurred in 28 (89%) of cases, pyrexia in 17 (53%) and ileus or abdominal pain in 14 (44%). Six patients responded to discontinuation of antibiotics alone and 22 required metronidazole and/or vancomycin. Three patients had colectomy and one caecostomy because of toxic megacolon. Four patients died before specific therapy could be given and in two of these cases the diagnosis was made at autopsy. Twenty-six patients had a record of recent antibiotic therapy. Of these, 15 had at least one agent considered to be inappropriate (excessively broad spectrum agent in 11, excessive duration of therapy in four). Nine patients had only received antibiotics prior to admission. CONCLUSIONS: CDAD carries a high mortality in nephrology patients, especially those with established CRF. The diagnosis may be missed if a careful antibiotic history is not taken, including agents received prior to admission. Rational antibiotic prescribing and adherence to infection control measures are vital to reduce the incidence of this serious condition.
Complications associated with insertion of jugular venous catheters for hemodialysis: the value of postprocedural radiograph.
It is routine in hemodialysis units to require a chest radiograph after the insertion of an internal jugular line for venous access before dialysis is commenced. There are two principal reasons for this: (1) to ensure that no procedural complications have occurred and (2) to verify correct catheter placement. Knowledge of the time delay involved may prompt nephrologists to opt for femoral access (with increased hemodialysis recirculation and need for repeated line placement). The benefit of the postprocedural chest radiograph has never been evaluated in the hemodialysis population. We retrospectively reviewed the data on internal jugular access placement from two large nephrology training centers. Over a 36-month period, 460 internal jugular dialysis catheters were placed in 312 patients. Wherever possible, 15-cm lines were used for the left internal jugular vein and 12-cm lines for the right internal jugular vein. Ultrasound guidance was used in 105 cases (22.8%). There were a total of 90 (19.6%) clinical complications in 62 patients (13.5%). These consisted of carotid artery puncture (n = 35, 7.6%) and hematoma (n = 55, 12%). All of these patients had a normal post-internal jugular chest radiograph. Carotid artery puncture did not occur if ultrasound guidance was used. There was no case of associated pneumothorax. Of the 370 line insertions in 250 patients in whom it was believed clinically that no complication had occurred, the chest radiograph only showed unsuspected line malposition in four cases (1.08%). Routine chest radiographs rarely contribute to the diagnosis of any procedural complications and are of little value after internal jugular access placement, especially if it is believed clinically that no complication occurred.
Cutaneous abnormalities and metabolic disturbance of porphyrins in patients on maintenance haemodialysis.
Blistering disorders may occur in patients with chronic renal failure. Photoactive medication may account for some, and others may be attributable to porphyria cutanea tarda (PCT), but most appear idiopathic. Seventy haemodialysis patients at the National Renal Transplant Centre were therefore screened to determine the prevalence of cutaneous disease and to establish a reference range for plasma porphyrins in this population. The possible contribution of hepatitis C virus (HCV) infection to increased porphyrin levels in this group was also investigated. Ninety four percent of patients on haemodialysis had dermatoses associated with chronic uraemia, and the plasma porphyrin levels in those patients (mean +/- 2 S.D.: 19.1 +/- 13.5 nmol/L) were significantly higher than those of a normal population (n = 40; mean +/- 2 S.D.: 5.5 +/- 3.2 nmol/L) (p < 0.05). Only 2 patients (2.9%), however, had antibodies to HCV and although three others had blistering on light-exposed skin, none of these had PCT or was on photoactive medication, nor did they differ from the rest of the haemodialysis population with regard to erythropoietin or alcohol ingestion. For patients on haemodialysis, therefore, in whom urinary porphyrin estimation is impossible or unreliable, it is recommended that plasma porphyrin profiles be checked where necessary with reference to the range for a haemodialysis population, in addition to assessment of the faecal porphyrin profile. Abnormal porphyrin levels in this group may not, however, be explained by HCV infection, but the occurrence of blistering on the sun-exposed sites of 3 patients suggests that ultraviolet radiation may be implicated in those instances.
Hepatitis E virus antibody prevalence.
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Hypercalcaemia due to squamous cell carcinoma in a tuberculous kidney: case report and review of pathogenesis.
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Haemostatic, fibrinolytic and endothelial variables in normal pregnancies and pre-eclampsia.
OBJECTIVE: To determine the behaviour of the coagulation variables antithrombin III (ATIII), protein C, thrombin/antithrombin III (TATIII); fibrinolytic activity, tissue plasminogen activator antigen (t-PA), plasminogen activator inhibitors (PAI) 1 and 2, and endothelial involvement by fibronectin assay in normal and pre-eclamptic pregnancies. DESIGN: Longitudinal and cross-sectional observational study. SETTING: Antenatal clinic and maternity hospital. SUBJECTS: Thirty-six primigravid normotensive caucasian patients, four of whom subsequently developed pre-eclampsia, and 12 patients with established pre-eclampsia. MAIN OUTCOME MEASURES: Plasma levels of PAI-1, PAI-2 and t-PA antigen were determined using an ELISA technique as were TATIII complex levels of fibronectin. ATIII and protein C plasma levels were assayed using chromogenic substrate techniques. RESULTS: PAI-1 and PAI-2 antigen levels rose progressively throughout normal pregnancy. Among the established pre-eclamptic group compared with matched normal pregnancies, the PAI-2 antigen level was significantly lower (48.5 +/- 22.8 versus 183.5 +/- 37.4; P < 0.001), the PAI-1 antigen level was significantly higher (122 +/- 34.4 versus 79.2 +/- 19.7; P < 0.001), ATIII activity was significantly lower (87.8 +/- 27.1 versus 110.9 +/- 19.3; P < 0.001) and TATIII complex levels were significantly higher (16.9 +/- 6.4 versus 10.2 +/- 5.9; P < 0.001). Among the four initially normotensive patients who subsequently developed pre-eclampsia, fibronectin levels were significantly elevated from as early as nine weeks of gestation. CONCLUSION: Significantly elevated levels of PAI-1 and fibronectin occurring early in pregnancies that subsequently develop pre-eclampsia suggest that these variables may have predictive values. PAI-2 would seem to be a marker of placental function in pre-eclampsia while increased t-PA and TATIII complex levels reflect the severity of the condition.
Sixth nerve palsy: an unusual manifestation of preeclampsia.
BACKGROUND: Neurologic abnormalities may occur in pregnancy as a manifestation of neurologic or systemic disease. We present an unusual case of preeclampsia presenting with a sixth nerve lesion. CASE: A 33-year-old woman, gravida 2, presented at 38 weeks' gestation with sixth nerve palsy. She was hypertensive and proteinuric, with plasma urea of 24 mg/dL. Labor was induced and hypertension escalated in the early puerperium, with concomitant worsening diplopia. Blood pressure control and resolution of preeclampsia were followed by resolution of the sixth nerve lesion. There was no evidence of other pathology on extensive investigations. CONCLUSION: Sixth nerve palsy is an unusual manifestation of preeclampsia.
Characteristics of bacteriuria in a homogeneous maternity hospital population.
Bacteriuria and urinary tract infection are a common cause of morbidity in pregnancy. Recent evidence has, however, questioned the magnitude of this risk and the effectiveness of therapy in reducing it. To clarify matters, a prospective study on 3123 ante-natal women was carried out. Screening for bacteriuria was carried out by culturing a mid-stream specimen of urine. Treatment was given to all patients with a positive culture and was based on antibiotic sensitivity testing. Repeat culture was performed 1 week after completion of therapy. The prevalence of bacteriuria in our population was 4.74%. Over half of these patients were asymptomatic. 67% of those with bacteriuria at screening were symptomatic or had a past history of urinary tract infection. Escherichia coli was the predominant organism cultured. The most effective antibiotic was Nitrofurantoin, which was sensitive in over 90% of isolates. Late urinary tract infection occurred in 3.52% of patients. There was no increase in maternal or foetal complications amongst those with bacteriuria. We concluded that it might be more cost-effective to confine screening to those patients who are symptomatic or have a past history of urinary tract infection.
Systemic lupus erythematosus and antiphospholipid antibodies in pregnancy--a case report and review of the literature.
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Clinical application of ambulatory blood pressure measurement in pregnancy.
Eclampsia and pre-eclampsia are the most important obstetric causes of maternal mortality in the Western world. The current definitions of hypertensive disorders in pregnancy rely on arbitrary blood pressure limits based on intermittent clinic readings which are subject to bias and error. Twenty-four-hour ambulatory blood pressure monitoring can overcome many of these deficiencies but has only recently been introduced into antenatal care. Five pregnancy studies using ambulatory blood pressure monitoring are currently underway in Birmingham, Glasgow, Grenoble, Oxford and Dublin. The results so far indicate that ambulatory blood pressure monitoring is an acceptable method of measuring blood pressure in pregnancy. It is also concluded that ambulatory blood pressure monitoring may have several roles in the future antenatal management of hypertension, including modification of existing classification systems, a clinical confirmatory role and a possible predictive role for pre-eclampsia.
Extracorporeal regional complexing haemodialysis treatment of acute inorganic mercury intoxication.
A 70-year-old white female presented approximately 24 h after ingesting three 475 mg tablets (1.425 g) of mercuric chloride in a suicide attempt. Acute renal failure necessitated the initiation of haemodialysis approximately 4 d after the ingestion. Treatment with BAL (2,3-dimercaptopropanol) resulted in only small increases in mercury output into dialysate. A new procedure involving the extracorporeal infusion of the chelating agent dimercaptosuccinic acid (DMSA) into the arterial blood line during haemodialysis was initiated. This procedure of Extracorporeal Regional Complexing Haemodialysis (ERCH) had been effective in increasing methylmercury removal in patients poisoned by contaminated grain. The first DMSA-ERCH procedure was performed 6 d after poisoning. There was a dramatic increase in mercury output into the dialysate. During three treatment sessions of 80 min each, 1189 micrograms of mercury were removed from the patient. The dialysed mercury represented the only mercury output since the patient was anuric and not producing faeces. DMSA-ERCH appears to be much more effective than BAL and haemodialysis in the treatment of acute inorganic mercury poisoning. The long interval between poisoning and initiation of treatment probably contributed to the patients ultimate demise, 28 d after poisoning. Efficacy of the DMSA-ERCH procedure for inorganic mercury poisoning is likely to be improved as the interval between exposure and treatment is reduced.
Prevalence of hereditary renal disease.
Little information is available concerning hereditary renal disease in the Irish population. We studied the prevalence and types of hereditary renal disease that lead to end stage renal failure by looking at the underlying hereditary disease in our dialysis populations and in all patients transplanted at the national unit. Twenty eight (15.7%) of 178 dialysis patients had hereditary renal disease with a mean age of 31 years (range nine to 65), and a male to female ratio of 1.54:1. Eighty-nine of 842 patients (10.3%) with renal transplants had hereditary renal disease with a male to female ratio of 1.63:1. The commonest entity was autosomal dominant polycystic kidney disease (68% in dialysis patients, 64% in transplants), and the next most frequent was Alport's syndrome (21.4%, 16.9%). Nephronophthisis was the third most common problem (10.7%, 10.1%) followed by hereditary non-Alport's nephritis, Fabry's disease, cystinosis and familial interstitial nephritis. The high prevalence of hereditary renal disease among the dialysis and renal transplant population emphasises the need for proper registration of the nature of renal disease in this group, and for a comprehensive genetic counselling service in this country.