M A Goldberg

Treatment of Sickle Cell Anemia with Hydroxyurea and Erythropoietin

BACKGROUND Hydroxyurea increases the production of fetal hemoglobin (hemoglobin F) in patients with sickle cell anemia and therefore has the potential for alleviating both the hemolytic and vaso-occlusive manifestations of the disease. There is preliminary evidence that recombinant human erythropoietin may also increase hemoglobin F production. METHODS AND RESULTS We treated five patients with sickle cell disease with escalating doses of intravenous erythropoietin for eight weeks. Three of these patients were subsequently treated with daily doses of oral hydroxyurea. After the optimal dose was determined, erythropoietin was then given along with hydroxyurea for four weeks. Treatment with erythropoietin, either alone or in combination with hydroxyurea, had no significant effect on the percentage of hemoglobin F-containing reticulocytes (F reticulocytes) or red cells (F cells). In contrast, hydroxyurea treatment was associated with a 3-to-25-fold increase in F reticulocytes, a 1.6-to-7-fold increase in F cells, and a 2.3-to-16-fold increase in the percentage of hemoglobin F. In all three patients given hydroxyurea, treatment with this drug was associated with reduced hemolysis, shown by decreases in serum bilirubin and lactic dehydrogenase and prolongation of red-cell survival. Hydroxyurea treatment also resulted in a decrease in the percentage of irreversibly sickled cells and sickling at partial oxygen saturation, an increase in oxygen affinity and total red-cell cation content, and a reduction in potassium-chloride cotransport. All three patients had a decrease in the number of pain crises. CONCLUSIONS This study confirms that hydroxyurea therapy increases hemoglobin F production and provides objective evidence that hydroxyurea reduces the rate of hemolysis and intracellular polymerization of hemoglobin S. In contrast, recombinant human erythropoietin, whether alone or in combination with hydroxyurea, offers no measurable benefit.

Enhancement of desynchronized sleep signs after pontine microinjection of the muscarinic agonist bethanechol

The question of which brainstem neuronal receptors can mediate cholinergic REM sleep induction was investigated by injecting the pure muscarinic agonist bethanechol via glass micropipettes in the pontine tegmentum of cats. The REM sleep enhancement was observed to be equally potent, equally dose-dependent and its appearance equally site-dependent as that previously observed with carbachol, a mixed muscarinic/nicotinic agonist. The results suggest that the pharmacological activation of muscarinic receptors in pontine neurons is sufficient to trigger REM sleep.

US, CT, and MRI of primary and secondary liver lymphoma.

Objective To describe the imaging findings in patients with pathologically proven hepatic lymphoma. Materials and Methods Ultrasound, CT, and MRI studies in 23 patients with primary (11 patients) or secondary (12 patients) liver lymphoma were retrospectively reviewed. All patients had proven non-Hodgkin lymphoma; all imaging studies were obtained within 3 weeks of biopsy. Results No finding or group of findings was specific for the diagnosis of hepatic lymphoma. In 7 of 11 cases of primary lymphoma, a single well-defined lesion was seen. Secondary liver lymphoma occurred as multiple (8 of 12) or diffusely infiltrating lesions (3 of 12) in most cases; it appeared as a solitary lesion in only 1 case. When discrete focal lesions were identified, the lesions were hypo- to anechoic on ultrasound, hypodense on CT, and had low and high signal intensity on TI- and T2-weighted MRI, respectively. Conclusion Although no one finding appears to be diagnostic of hepatic lymphoma, ultrasound that demonstrates a homogeneous, hypoechoic, through-transmitting lesion combined with CT that demonstrates a solid, low attenuation lesion is highly suggestive of primary liver lymphoma. Secondary liver lymphoma can have a greater variety of appearances and is more likely to be multiple or diffusely infiltrating lesions than a solitary lesion.

FDG PET characterization of renal masses : Preliminary experience

OBJECTIVE This study was undertaken to evaluate the potential efficacy of fluorine-18 2-fluoro-2-deoxy-D-glucose positron emission tomography (FDG PET) to detect renal tumours and to characterize indeterminate renal cysts. SUBJECTS AND METHODS Twenty-six PET scans were performed in 21 patients (14 PET scans in 10 patients with malignant renal tumours and 12 PET scans in 11 patients with Bosniak type 3 indeterminate renal cysts). Pathological proof was obtained in 18 of 21 patients (10 with solid neoplasms, eight with indeterminate cysts). Imaging was performed 1 h after injection of 5-10 mCi of FDG with IV administration of Lasix (10 mg) 20 mins after injection. Two consecutive 9.7-cm image segments were scanned to cover the entire renal areas. RESULTS PET accurately depicted solid neoplasms as areas of increased uptake in nine of 10 patients. Bilateral renal cell carcinomas were missed in one diabetic patient. All but one indeterminate renal cysts were correctly classified as benign (photopenic areas), but an indeterminate cyst with a 4-mm papillary neoplasm was wrongly classified as benign. There were no false positive PET interpretations. The mean tumour-to-kidney ratio was 3.0 for malignant lesions. CONCLUSION We conclude that FDG PET scanning shows promise in the evaluation of indeterminate renal cysts. A positive PET scan in the appropriate clinical setting obviates the need for cyst aspiration. A negative PET scan in conjunction with a negative cyst aspiration offers confirmatory evidence of benignity. Our preliminary results are encouraging and further work is ongoing.

Failed metallic biliary stents: Causes and management of delayed complications

OBJECTIVE To describe the incidence, management and long-term outcome of metal stent failure in patients with malignant biliary obstruction. SUBJECTS AND METHODS Sixty-nine patients received a total of 93 metallic biliary stents for relief of malignant biliary obstruction. Twenty-nine patients had hilar tumours; 40 had common bile duct tumours. RESULTS Ten of 69 patients (14%) presented with stent occlusion at a mean interval of 4 months after stent insertion. Five of 29 patients (17%) with hilar lesions and five of 40 patients (12%) with common bile duct lesions had stent occlusion. Occlusion was due to tumour overgrowth in eight patients and to occlusion by debris in two. The eight patients with tumour overgrowth were treated with internal/external catheters (5 patients), no therapy (2 patients), and further metal stents (1 patient). These eight patients with tumour overgrowth had a limited lifespan after tumour overgrowth occurred with a mean survival of 2.6 months. The two patients with occlusion due to debris were treated by sweeping the stent with a balloon catheter and these patients survived 26 and 27 months, respectively. CONCLUSION Adequate peripheral purchase in the biliary tree and overstenting are necessary to prevent tumour overgrowth when stenting hilar lesions. The development of stent occlusion due to tumour overgrowth heralds a limited survival and internal/external catheters are preferred over further metal stents for palliation.

Comprehensive Health Care Reform and Managed Competition

The debate about health care reform is under way, and for that we should all be grateful. There is little question that reform is needed to control costs, ensure access for the tens of millions of ...

Gadolinium-DTPA enhanced echoplanar MR imaging of the liver: Preliminary observations

This study describes our preliminary experience with dynamic gadopentetate dimeglumine enhanced echoplaner MR imaging (EPI) in fifteen patients with focal liver lesions. Lesion diagnosis was established by histology (n = 3) or typical imaging characteristics (exclusive of the EPI study) combined with clinical follow up (n = 12). Dynamic gadopentetate dimeglumine (0.1 mmol/kg) enhanced MR imaging was performed on a commercially available 1.5 T EPI equipped MR system using a single-excitation fat-suppressed inversion recovery pulse sequence. The choice of an IR sequence allowed nulling of the lesion signal by varying T1 prior to enhancement creating the optimal conditions for qualitative inspection of the enhancement profile. Intershot delay (defined as TR) ranged from 1-5s. Image analysis was performed qualitatively by two radiologists. Benign and malignant lesions displayed temporal enhancement profiles compatible with characteristic findings expected with conventional imaging modalities. Further refinements in our technique and expanded system capabilities will allow dynamic imaging of the entire liver with improved temporal resolution over conventional sequences.