Leukemia,lymphoma, and multiple myeloma following selected medical conditions

The role of selected prior medical conditions in the etiology of hematopoietic malignancies was examined in a case-control study of members of two regional branches of the Kaiser Permanente Medical Care Program (USA). Past history of chronic infectious, autoimmune, allergic, and musculoskeletal disorders was abstracted from medical records for leukemia (n = 299), non-Hodgkin's lymphoma (NHL, n = 100), and multiple myeloma (n = 175) cases and matched controls (n = 787). Little difference was found between cases and controls for most of the chronic conditions evaluated, including sinusitis, carbuncles, urinary tract infections, pelvic infections, herpes zoster, asthma, rheumatoid arthritis, psoriasis, bursitis, and gout. Only three statistically significant elevated risks were found, i.e., with combined disc disease myeloma among patients with prior eczema and disk and other musculoskeletal conditions, and NHL following tuberculosis. Only two of these associations showed consistent patterns by sex and geographic region (myeloma with eczema and with musculoskeletal conditions). While prior history of eczema and musculoskeletal conditions may slightly increase risk of myeloma, this study provided little if any support for an association of chronic infectious, autoimmune, allergic, and musculoskeletal conditions with subsequent occurrence of the leukemias or NHL. Additionally, these data did not support a role for chronic antigenic stimulation, as defined in previous epidemiologic studies, in the etiology of hematopoietic malignancies.Ms Doody and Drs Linet, Pottern, Boice, and Fraumeni are with the Epidemiology and Biostatistics Program, National Cancer Institute. Dr Glass is with the Kaiser Permanente Medical Care Program, Northwest Region, Portland, Oregon, USA. Dr Friedman is with the Kaiser Permanente Medical Care Program, Northern California Region, Oakland, California, USA. Address correspondence to Ms Doody, Radiation Epidemiology Branch, National Cancer Institute, Executive Plaza North, Room 408, Bethesda, MD 20892, USA. This research was supported in part by National Cancer Institute contracts NO1-CP-01047, NO1-CP-01054, NO1-CP-11009, NO1-CP-11037, NO1-CP-31035, and NO1-CP-61006.     

Successful Treatment of Kasabach-Merritt Syndrome with Prednisone and Epsilon-Aminocaproic Acid

The Kasabach-Merritt syndrome is characterized by thrombocytopenia and localized coagulopathy associated with a hemangioma. Most techniques applied to eradicate the tumor or accelerate its involution (surgery, radiation therapy, embolization) are invasive and require transfusion of large amounts of blood products. In some cases, medical treatment is the only alternative. Efficacy of steroids and antifibronolytic agents has already been described, but even this approach is associated with the administration of blood products. We report two cases of infants with Kasabach-Merritt syndrome associated with cardiac and hepatic hemangiomas. At admission, both had signs of cardiac failure. They were successfully treated with prednisone and epsilon-aminocaproic acid (EACA). Blood products were not required once the diagnosis was made. These observations have important implications for the management of patients with Kasabach-Merritt syndrome because they show that even in severe cases blood transfusions can be avoided by the use of prednisone and EACA.     

Anosognosia in mild cognitive impairment: Relationship to activation of cortical midline structures involved in self-appraisal.

Awareness of cognitive dysfunction shown by individuals with Mild Cognitive Impairment (MCI), a condition conferring risk for Alzheimer's disease (AD), is variable. Anosognosia, or unawareness of loss of function, is beginning to be recognized as an important clinical symptom of MCI. However, little is known about the brain substrates underlying this symptom. We hypothesized that MCI participants' activation of cortical midline structures (CMS) during self-appraisal would covary with level of insight into cognitive difficulties (indexed by a discrepancy score between patient and informant ratings of cognitive decline in each MCI participant). To address this hypothesis, we first compared 16 MCI participants and 16 age-matched controls, examining brain regions showing conjoint or differential BOLD response during self-appraisal. Second, we used regression to investigate the relationship between awareness of deficit in MCI and BOLD activity during self-appraisal, controlling for extent of memory impairment. Between-group comparisons indicated that MCI participants show subtly attenuated CMS activity during self-appraisal. Regression analysis revealed a highly significant relationship between BOLD response during self-appraisal and self-awareness of deficit in MCI. This finding highlights the level of anosognosia in MCI as an important predictor of response to self-appraisal in cortical midline structures, brain regions vulnerable to changes in early AD.     

Is early onset cerebellar ataxia with retained tendon reflexes identifiable by electrophysiologic and histologic profile? A comparison with Friedreich's ataxia.

An electrophysiologic and histologic study was performed on 18 patients affected by early onset cerebellar ataxia with retained tendon reflexes (EOCA). Sensory and motor conduction velocity (SCV, MCV) was measured along peripheral nerves in all patients, somatosensory (SSEP) and brainstem auditory evoked potentials (BAEP) were recorded in 13; cortical stimulation (CS) in 12, and sural nerve biopsy in 4 patients were also performed. The results as a whole allow a division of EOCA patients into 2 groups: with (7 patients) and without (11 patients) peripheral neuropathy. Among EOCA patients with neuropathy a differential diagnosis with Friedreich's disease patients was not possible according to BAEPs and CS, while SSEPs could differentiate 2 out 5 patients in whom they were performed.     

Forthcoming meetings & events

Forthcoming meetings &; events     

Heart rate changes in chronic insomnia

This study assessed physiological activity in patients with chronic insomnia before sleep, during sleep and in response to acute stress. Twenty-four subjects with chronic insomnia and 25 normal sleepers slept in the laboratory overnight and were given a stressful performance task in the morning. Heart rate was significantly higher in the insomniac group at night. The next morning, heart rate was not different at baseline, but was significantly higher during the performance task in the insomniac group. These results are discussed as supporting the notion that insomniacs have greater physiological responsivity to stress. Further research is needed to determine if altered physiological activity is a cause or consequence of insomnia.     

Nursing grand rounds: multiple sclerosis.

Multiple sclerosis (MS) is a highly variable, unpredictable disease and one of the most life-altering diagnoses a person can receive. Because it usually strikes in the prime of life, frequently progresses to disability, and has no cure, MS can make a strong emotional impact--not only on those who suffer from it, but also the healthcare team. Because MS is such a complex, multifaceted disorder, nurses who care for people with MS are faced with numerous clinical challenges. Many of the challenges are unique to MS, demanding, and time-consuming. Well-informed nurses are positioned to evaluate and explain the disease process, assist in the alleviation of symptoms, educate partners and families, and help improve quality of life. A case example can help nurses understand the real-life concerns of a person with MS.     

The late growth hormone rise induced by oral glucose is enhanced by cholinergic stimulation with pyridostigmine in normal subjects

OBJECTIVE: We have investigated the late GH rise occurring 3-5 hours after oral glucose administration. We have assessed the effect of endogenous cholinergic enhancement with pyridostigmine on the delayed GH rise following oral glucose loading in normal subjects. DESIGN: Placebo or 75 g oral glucose was given to the normal subjects 3 hours before 120 mg oral pyridostigmine or placebo. Four tests were carried out at random. (0 min) + placebo (180 min); test 2: glucose (0 min) + placebo (180 min); test 3: placebo (0 min) + pyridostigmine (180 min); test 4: glucose (0 min) + pyridostigmine (180 min). SUBJECTS: We studied eight normal subjects (four male and four female), ages 19-29 years, body mass indices 18-22 kg/m2. MEASUREMENTS: Plasma glucose and serum GH concentrations were measured for 6 hours after oral glucose or placebo administration. RESULTS: Pyridostigmine treatment significantly enhanced the GH releasing effect of prior (3 h) oral glucose. Late GH peak obtained by oral glucose loading rose from (mean +/- SEM) 17.4 +/- 4.6 to 37.2 +/- 9.0 mU/l (P < 0.05) after pyridostigmine, while GH peak following placebo plus pyridostigmine was 12.4 +/- 2.0 mU/l (P < 0.05 vs glucose plus pyridostigmine). The analysis of GH area under curves (AUCs) in the second phase of the tests (180-360 min) confirmed that glucose plus pyridostigmine released a greater amount of GH (4128 +/- 764 mU/l/3h) than glucose (1694 +/- 494 mU/l/3h, P < 0.001) or pyridostigmine alone (1292 +/- 150 mU/I/3h, P < 0.001). CONCLUSIONS: Pyridostigmine, an indirect cholinergic drug likely to inhibit somatostatin secretion from the hypothalamus, enhanced the late GH releasing activity of oral glucose. There is evidence that glucose suppresses plasma GH initially by increasing hypothalamic somatostatin release. This would result in an increase in the pituitary stores of GH. We propose that the delayed GH rise after oral glucose occurs when there is a fall in hypothalamic somatostatinergic tone; this is further reduced by the administration of pyridostigmine. At this time the pituitary stores of GH are released as a consequence of resumption of hypothalamic GHRH activity. This leads to the late GH rise.