Conventional and experimental drug therapy in myelofibrosis with myeloid metaplasia

Myelofibrosis with myeloid metaplasia (MMM) is currently classified as a classic (ie, BCR-ABL-negative) myeloproliferative disorder characterized by anemia, multiorgan extramedullary hematopoiesis, constitutional symptoms, and premature death from either leukemic transformation or other disease complications. Stem cell transplantation can be curative, but many patients either are not appropriate candidates or do not choose to accept the significant risks associated with transplantation. Current pharmacologic therapy has been beneficial mainly in terms of palliating disease-associated cytopenias, constitutional symptoms, splenomegaly, and other organ damage from excess myeloproliferation. Novel treatment strategies are under investigation, including targeted inhibition of JAK2^V617F, the activating tyrosine kinase point mutation present in about half of patients with MMM. In this article, we review both the old and new pharmacologic options for MMM.     

Unilateral pseudobulbar syndrome with limited capsulothalamic infarction

A unilateral pseudobulbar syndrome consequent to unilateral capsulothalamic infarction is described. Motor deficit of the face was associated with marked velar and pharyngeal unilateral palsy; paresis of limbs was mild. ACT scan revealed a circumscribed infarction of the genu of the internal capsule. This raised the problem of unilateral supranuclear pharyngeal palsies and of the precise anatomy of the genicular tract in the genu of the internal capsule.     

CT-guided brachial plexus biopsy.

We describe a technique for conducting a CT-guided biopsy of the brachial plexus region, report two illustrative cases, discuss potential complications, and conclude that, in selected cases, biopsy of lesions in the region of the brachial plexus can be performed safely with CT guidance.     

Pheochromocytoma and paraganglioma: comparison of MR imaging with CT and I-131 MIBG scintigraphy

To ascertain the magnetic resonance (MR) imaging characteristics of pheochromocytomas and paragangliomas and to compare MR with computed tomography (CT) and iodine-131 metaiodobenzylguanidine (I-131 MIBG), 19 patients (18 with pheochromocytomas, one with a paraganglioma) were studied. The 18 patients with pheochromocytomas had had positive findings with I-131 MIBG scintigraphy. Abdominal pheochromocytomas were generally hypointense compared with normal liver on T1-weighted MR images and extremely hyperintense on T2-weighted MR images. MR imaging was preferable to CT in the evaluation of primary pheochromocytomas due to superior tissue characterization, particularly in the patient with hypertension and borderline catecholamine levels. For patients with recurrent or metastatic disease, the data suggest that I-131 MIBG scintigraphy is the examination of choice.     

Cost-effectiveness of coronary artery bypass surgery in octogenarians.

OBJECTIVE: The objective of this retrospective cohort study was to determine whether coronary artery bypass graft (CABG) surgery is effective and cost-effective relative to medical management of coronary artery disease (CAD) in the elderly. SUMMARY BACKGROUND DATA: The aging of the U.S population and the improvements in surgical techniques have resulted in increasing numbers of elderly patients who undergo this surgery. The three randomized, controlled trials (RCTs) that established the efficacy of CABG surgery completed patient enrollment from 19 to 24 years ago excluded patients older than 65 years. Although information regarding outcomes of CABG in this population is mainly available in case series, a major lacuna exists with respect to information on quality of life and cost effectiveness of surgery as compared with medical management. METHODS: The authors retrospectively formed surgical and medically managed cohorts of octogenarians with significant multivessel CAD. More than 600 medical records of patients older than 80 years who underwent angiography at our institution were reviewed to identify 48 patients who were considered reasonable surgical candidates but had not undergone surgery. This cohort was compared with 176 patients who underwent surgery. RESULTS: The cost per quality-adjusted life year saved was $10,424. At 3 years, survival in the surgical group was 80% as compared with 64% in the entire medical cohort and 50% in a smaller subset of the medical cohort. Quality of life in patients who underwent surgery was measurably better than that of the medical cohort with utility index scores, as measured by the EuroQoL, (a seven-item quality of life questionnaire) of 0.84, 0.61, and 0.74, respectively. CONCLUSIONS: Performing CABG surgery in octogenarians is highly cost-effective. The quality of life of the elderly who elect to undergo CABG surgery is greater than that of their cohorts and equal to that of an average 55-year-old person in the general population.     

High prevalence of human papillomavirus infections in urine samples from human immunodeficiency virus-infected men

Infection with human immunodeficiency virus (HIV) and the resulting immunosuppression are associated with an increased risk for human papillomavirus (HPV) persistence and related malignancies. In the present study we investigated the prevalence of HPV in urine samples from 104 HIV-infected men with low CD4+ cell counts (<100 per mm(3)) and 115 urine samples from HIV-negative men. A high prevalence of HPV DNA (39.4%) was found in the HIV patients. Most of the HPV types were high risk (81.4%), with HPV 52 as the most prevalent type (12.5%), followed by HPV 18 (6.7%), HPV 35 (5.8%), and HPV 70 (4.8%). Multiple HPV genotypes were observed in 17 (41%) of the 41 HPV- and HIV-positive men. In contrast, only 11 (9.6%) HPV DNA-positive cases were observed among the 115 HIV-uninfected men, and 3 (27.3%) contained multiple genotypes. Quantitative analyses indicated that the HPV viral load, as measured in urine samples, is significantly higher in HIV-positive men compared to HIV-negative men. In the present study we show that urine samples are useful for detecting HPV DNA, there is a high prevalence of HPV in HIV-positive men, and the HPV viral load is substantially higher in HIV-positive than in HIV-negative men. More studies are needed to evaluate the risk and natural development of HPV-related malignancies in HIV-positive men.     

Dietary micronutrients/antioxidants and their relationship with bronchial asthma severity

BACKGROUND: Because little is known about micronutrient/antioxidant intake and asthma severity, we investigated dietary intake and plasma/serum levels of micronutrients/antioxidants in a group of asthma patients with various degrees of severity, and compared the results with healthy subjects. METHODS: A case control study was carried out on 118 asthma patients and 121 healthy subjects. The severity of the disease was classified by division of patients into four groups. Normal dietary micronutrient/antioxidant intake was estimated from a food frequency questionnaire. Plasma/serum levels of vitamins C, E, and A, selenium, magnesium, zinc, and platelet glutathione peroxidase (GSH-Px) activity were also determined. RESULTS: No differences in daily micronutrient/antioxidant intake were seen between patients and healthy subjects. The severity of the disease showed no significant relationship with micronutrient/antioxidant intake. There were no differences in plasma/serum levels in any of the micronutrients/antioxidants between healthy subjects and asthmatics. Nor were any differences found between asthma groups in severity in the biochemical measures, except in platelet GSH-Px activity, which was significantly lower in the most severe groups. CONCLUSIONS: In this study, we found no evidence of any association between micronutrient/antioxidant intake or plasma/serum levels of micronutrients/antioxidants and asthma. Reduction of platelet GSH-Px activity in the most severe patients suggests that these patients have a diminished capacity to restore part of the antioxidant defences.     

Comparison of magnetic resonance imaging and ultrasonography in staging early prostate cancer. Results of a multi-institutional cooperative trial

BACKGROUND. In 1987, a cooperative study group consisting of five institutions was formed to determine the relative benefits of magnetic resonance imaging (MRI) and endorectal (transrectal) ultrasonography in evaluating patients with clinically localized prostate cancer (stage Ta or Tb). METHODS. Over a period of 15 months, 230 patients were entered into the study and evaluated with identical imaging techniques. We compared imaging results with information obtained at the time of surgery and on pathological analysis. RESULTS. MRI correctly staged 77 percent of cases of advanced disease and 57 percent of cases of localized disease; the corresponding figures for ultrasonography were 66 and 46 percent (P not significant). These figures did not vary significantly between readers; moreover, simultaneous interpretation of MRI and ultrasound scans did not improve accuracy. In terms of detecting and localizing lesions, MRI identified only 60 percent of all malignant tumors measuring more than 5 mm on pathological analysis and ultrasonography identified only 59 percent. CONCLUSIONS. The MRI and ultrasonography equipment that is currently available is not highly accurate in staging early prostate cancer, mainly because neither technique has the ability to identify microscopic spread of disease. Further evaluation with improved equipment may improve the accuracy of these techniques.