Erythropoietin deficiency and relative resistance cause anaemia in post-renal transplant recipients with normal renal function

BACKGROUND: Following successful renal transplantation, blood erythropoietin(Epo) levels peak in two phases during the first 2–3 months,and blood haemoglobin/haematocrit (Hb/Hct) levels are restoredto normal in a period of 2–6 months. However, some transplantrecipients continue to remain anaemic in spite of normal graftfunction and in the absence of recognizable causes. The roleof endogenous Epo production in the causation of anaemia insuch patients is poorly understood and has been investigatedin this study. METHODS: Twenty-three post-renal transplant recipients with stable normalrenal function were studied. Eleven of these patients had normalHb/Hct levels (group 1) and served as control for the rest 12patients with anaemia (group 2). Patients included in group2 had no readily recognizable cause for their anaemia. Otherlaboratory and clinical findings were similar in both groups.Patients with erythrocytosis were excluded. Serum Epo levelswere measured in all patients. Five patients in group 2 weretreated with recombinant human erythropoietin (rHuEpo) and theirerythropoietic response was assessed. rHuEpo was discontinuedwhen the target Hb/Hct levels (lowest normal range) were achievedand the patients were followed up for a further period of 9–12months. RESULTS: Five patients in group 1 had normal expected serum Epo levelswhereas the other six patients had inappropriately high serumEpo levels with respect to their Hb/Hct status suggestive ofrelative ‘Epo resistance’. Serum Epo levels in allpatients except two in group 2 were low indicative of ‘Epodeficiency’. The two exceptional patients in group 2 hadhigher serum Epo levels in the presence of anaemia suggestiveof relative ‘Epo resistance’. All five patients treated with rHuEpo responded adequately byachieving normal Hb/Hct levels. Three of them were originally‘Epo deficient’ and they reached target Hb/Hct levelsin a mean period of 4 weeks, requiring a mean cumulative rHuEpodose of 428.3 units/kg. The other two patients with higher initialserum Epo levels, and considered to be ‘Epo resistant’,required an average of 11 weeks of treatment and a mean cumulativerHuEpo dose of 1582.5 units/ kg, indicating an increased Epodemand. On cessation of therapy the Hb/Hct levels fell in allfive patients to pretreatment values in 6 months. CONCLUSIONS: There are important variations in the endogenous Epo productionin renal transplant patients with normal renal function, thecause of which is not clear. Epo deficiency and relative Eporesistance play a causative role for anaemia in some post-renaltransplant recipients with stable normal renal function. Theyrespond adequately to rHuEpo administration.     

Application of technetium-99m hexamethylpropylene amine oxime single-photon emission tomography to neurologic prognosis in patients undergoing urgent carotid surgery

In this study we aimed to work out a quantitative prognostic index for preoperative assessment of brain technetium-99m hexamethylpropylene amine oxime (HMPAO) single-photon emission tomography (SPET) in patients referred for urgent carotid endarterectomy due to acute obstructive disease of the internal carotid artery (ICA) and neurological deficit. To this end we compared data from preoperative SPET studies with the postinterventional changes in neurological status in 20 patients (17 males, three females; mean age 53 years, SD 4 years) with acute ischaemic cerebral disorders induced by obstruction of the ICA. Carotid obstruction was diagnosed by ultrasound B-mode study. All patients underwent urgent carotid endarterectomy from the ICA. Patients were divided into two groups in accordance with the results of postoperative follow-up: group A comprised patients with significant (more than 3 points) postoperative improvement in neurological condition as quantified by the Canadian Neurological Scale (11 patients); group B consisted of patients with minimal improvement or deterioration (nine, three of whom died). All patients were studied preoperatively by^99mTc-HMPAO SPET. The volume of nonperfused tissue (VS, cm³) was quantified using the Mountz technique. Hypoperfused volume (V _hypoperf, cm³) in the affected hemisphere was calculated as the total volume of voxels with^99mTc-HMPAO uptake <90% of the contralateral symmetric voxels. Discriminant prognostic function was calculated by discriminant analysis as:PF = 0.072×VS + 29.46×(VS/V _hypoperf). Patients with preoperativePF values <8.20 demonstrated postoperative improvement in neurological status, while the group withPF>8.90 comprised patients who demonstrated minimal improvement or deterioration. PF values in the range 8.20–8.90 carried an indefinite prognosis. We conclude that the preoperative^99mTc-HMPAO SPET can be used for the selection of patients in whom improvement in neurological status may be expected after urgent surgical correction of acute extracranial obstruction of the ICA.     

Minimally Invasive Coronary Artery Bypass Grafting: A New Method Using an Anterior Mediastinotomy

The benefit of internal mammary artery (IMA) grafting as a long-lasting intervention for coronary artery disease is well recognized. However, largely because they are less invasive, catheter based alternatives are frequently chosen, particularly to treat single or double vessel disease. To retain the advantages of the IMA graft, and to offset the invasiveness of conventional coronary artery bypass grafting, we developed a new minimally invasive method using an anterior mediastinotomy for treating left anterior descending (LAD) or right coronary artery disease, or both. Feasibility studies using 16 pigs and a human cadaver led to approval by the Institutional Review Board for use of this procedure to treat six patients (four men, two women; mean age, 63.8 ± 13.6 [SD] yrs) who granted informed consent. Pedicle dissection of the IMA, using video assisted thoracoscopy if necessary, was made through a 2-to 3-inch horizontal anterior mediastinotomy. The underlying LAD artery was grafted during femoral vessel cardiopulmonary bypass, with cooling to 30°C, induced ventricular fibrillation, and left ventricular venting if required. Transesophageal echocardiography performed after bypass showed that two patients maintained normal wall motion and four had improvement from the original impairment. One patient suffered a recurrence of angina 4 weeks after the procedure; recatheterization showed an acutely angled IMA, subsequently corrected by balloon angioplasty. The results of follow-up dobutamine echocardiographic stress tests were negative in all patients. With this minimally invasive approach, the procedure should provide the benefits of IMA grafting with shorter hospital stay, more rapid recovery, and less overall cost.     

Management of hypothalamic gliomas in children: an analysis of 33 cases

The cases of 33 children with hypothalamic-chiasmatic gliomas are reviewed. Radiation therapy produced clinical or radiographic improvement in 11 (46%) of 24 patients. Progression was documented in 18 patients (54%). Overall, the median time to tumor progression was 60 months; it was 70 months in patients who received radiation therapy and 30 months in those who did not (P less than 0.05). Chemotherapy, either given initially or at the time of progression, caused the tumor to respond or to stabilize in 10 patients. Partial resection of the tumor led to improvement in 3 of 12 patients, obviating the need for a shunt in 2 of them; there were no deaths and postoperative morbidity was transient and minimal (diabetes insipidus, intraventricular hemorrhage, and left hemiparesis in one patient each). The 5- and 10-year survival probabilities were 93 and 74%, respectively. Patients with neurofibromatosis had a better prognosis.