A cross-sectional study of docosahexaenoic acid status and cognitive outcomes in females of reproductive age with phenylketonuria

Diet therapy for phenylketonuria (PKU) requires restricted phenylalanine (Phe) intake, with the majority of protein and other nutrients coming from synthetic medical food. The fatty acid docosahexaenoic acid (DHA) is important in brain development and function; however, there are reports of low blood DHA concentrations in people treated for PKU. Although the implications of this low blood DHA are unclear, subtle cognitive deficits have been reported in those treated early and continuously for PKU. For this study, we investigated the relationship between DHA status and cognitive performance in 41 females 12 years and older with PKU. Participants were attending the baseline visit of a research-based camp or a supplementation trial. We assessed the domains of verbal ability, processing speed, and executive function using standardized tests, and the proportions of DHA in plasma and red blood cell (RBC) total lipids using gas chromatography/mass spectrometry. Percent plasma and RBC total lipid DHA were significantly lower in the participants compared with laboratory controls (P < .001), and participants consumed no appreciable DHA according to diet records. Plasma and RBC DHA both negatively correlated with plasma Phe (P < .02), and performance on the verbal ability task positively correlated with RBC DHA controlling for plasma Phe (R = .32, P = .03). The relationship between DHA and domains related to verbal ability, such as learning and memory, should be confirmed in a controlled trial. Domains of processing speed and executive function may require a larger sample size to clarify any association with DHA.     

von Willebrand disease and other inherited bleeding disorders in women with diagnosed menorrhagia

OBJECTIVE: To estimate the prevalence of von Willebrand disease and other bleeding disorders in women with and without diagnosed menorrhagia. METHODS: Women with menorrhagia were identified among members of a health maintenance organization in the southeastern United States through a computer search for appropriate International Classification of Diseases, 9th Revision codes. A random sample of members with no such code was selected as controls. The study included 121 women with menorrhagia and 123 controls. Subjects were interviewed in person, and blood was drawn for coagulation testing. Laboratory results for menorrhagia patients were compared with those in controls using race and blood type specific ranges developed from the control group. A test was considered abnormal if it exceeded two standard deviations below the control mean. RESULTS: Bleeding disorders (von Willebrand disease, factor deficiency, or a platelet abnormality) were diagnosed in 10.7% of menorrhagia patients and 3.2% of controls (P =.02). von Willebrand disease was present in eight menorrhagia patients (6.6%) and in one control (0.8%) (P =.02); separate analyses by race revealed a von Willebrand disease prevalence of 15.9% among white and 1.4% among black menorrhagia patients (P =.01). Women with bleeding disorders did not differ significantly from controls in other symptoms of bleeding. CONCLUSION: The prevalence of inherited bleeding disorders among white women with menorrhagia was substantial, consistent with European data published recently. For unknown reasons, the prevalence of von Willebrand disease was lower among black women. These findings indicate the importance of considering inherited bleeding disorders as a cause of menorrhagia.     

Movement disorders in pregnancy

Movement disorders are not particularly common during pregnancy, with a few exceptions. RLS occurs most commonly followed by CG. Currently, with the incidence of rheumatic fever lower than previously, any woman who develops CG should be checked for illness other than rheumatic heart disease. The differential includes systemic lupus erythromatosis and antiphospholipid antibody syndrome. Regarding the use of dopaminergic agents, the dopamine agonist, pergolide, can be maintained during pregnancy for the treatment of PD, Segawa disease, and RLS. The use of levodopa and ropinirole should be limited during pregnancy because of the possible teratogenic effects. Amantadine is contraindicated during pregnancy. The data on selegiline are controversial; animal studies show possible serotonergic effects and teratogenic effects. If treatment is indicated in patients who have Tourette syndrome, the high potency neuroleptics drugs (haloperidol) are preferred to treat associated symptoms. Depression is a common comorbidity in patients who have PD, HD,Tourette syndrome, or other chronic neurologic diseases. Depression treatment during pregnancy is covered by Levy et al elsewhere in this issue. As discussed previously, most of the data on the use of drugs during pregnancy, especially the dopaminergic agents, are limited to animal studies and case reports. Therefore, it is in part left to the neurologist to decide on treatment based on the individual patient, clinical judgment, and inferences from animal studies and limited case reports.     

Dysautonomia rating scales in Parkinson's disease: Sialorrhea,dysphagia, and constipation—Critique and recommendations by movement disorders task force on rating scales for Parkinson's disease

Upper and lower gastrointestinal dysautonomia symptoms (GIDS)—sialorrhea, dysphagia, and constipation are common in Parkinson's disease (PD) and often socially as well as physically disabling for patients. Available invasive quantitative measures for assessing these symptoms and their response to therapy are time‐consuming, require specialized equipment, can cause patient discomfort and present patients with risk. The Movement Disorders Society commissioned a task force to assess available clinical rating scales, critique their clinimetric properties, and make recommendations regarding their clinical utility. Six clinical researchers and a biostatistician systematically searched the literature for scales of sialorrhea, dysphagia, and constipation, evaluated the scales' previous use, performance parameters, and quality of validation data (if available). A scale was designated “Recommended” if the scale was used in clinical studies beyond the group that developed it, has been specifically used in PD reports, and clinimetric studies have established that it is a valid, reliable, and sensitive. “Suggested” scales met at least part of the above criteria, but fell short of meeting all. Based on the systematic review, scales for individual symptoms of sialorrhea, dysphagia, and constipation were identified along with three global scales that include these symptoms in the context of assessing dysautonomia or nonmotor symptoms. Three sialorrhea scales met criteria for Suggested: Drooling Severity and Frequency Scale (DSFS), Drooling Rating Scale, and Sialorrhea Clinical Scale for PD (SCS‐PD). Two dysphagia scales, the Swallowing Disturbance Questionnaire (SDQ) and Dysphagia‐Specific Quality of Life (SWAL‐QOL), met criteria for Suggested. Although Rome III constipation module is widely accepted in the gastroenterology community, and the earlier version from the Rome II criteria has been used in a single study of PD patients, neither met criteria for Suggested or Recommended. Among the global scales, the Scales for Outcomes in PD‐Autonomic (SCOPA‐AUT) and Nonmotor Symptoms Questionnaire for PD (NMSQuest) both met criteria for Recommended, and the Nonmotor Symptoms Scale (NMSS) met criteria for Suggested; however, none specifically focuses on the target gastrointestinal symptoms (sialorrhea, dysphagia, and constipation) of this report. A very small number of rating scales have been applied to studies of gastrointestinal‐related dysautonomia in PD. Only two scales met “Recommended” criteria and neither focuses specifically on the symptoms of sialorrhea, dysphagia, and constipation. Further scale testing in PD among the scales that focus on these symptoms is warranted, and no new scales are needed until the available scales are fully tested clinimetrically. © 2009 Movement Disorder Society     

Occurrence of hemophilia in the United States

An active surveillance system was used to identify all residents with hemophilia in six U.S. states (Colorado, Georgia, Louisiana, Massachusetts, New York, and Oklahoma). A hemophilia case was defined as a person with physician-diagnosed hemophilia A or B and/or a measured baseline factor VIII or IX activity (FA) of 30% or less. Case-finding methods included patient reports from physicians, clinical laboratories, hospitals, and hemophilia treatment centers. Once identified, trained data abstractors collected clinical and outcome data retrospectively from medical records. Among cases identified in 1993–1995, 2,743 were residents of the six states in 1994, of whom 2,156 (79%) had hemophilia A. Of those with available FA measurements, 1,140 (43%) had severe (FA < 1%), 684 (26%) had moderate (FA 1%–5%), and 848 (31%) had mild (FA 6%–30%) disease. The mean and median age was 25.4 and 23 years, respectively. The age-adjusted prevalence of hemophilia in all six states in 1994 was 13.4 cases/100,000 males (10.5 for hemophilia A and 2.9 for B). The prevalence by race/ethnicity was 13.2 cases/100,000 among white, 11.0 among African American, and 11.5 among Hispanic males. Application of age-specific prevalence rates from the six surveillance states to the U.S. population resulted in an estimated national population of 13,320 cases of hemophilia A and 3,640 cases of hemophilia B. For the 10-year period 1982–1991, the average incidence of hemophilia A and B in the hemophilia surveillance system (HSS) states was estimated to be 1 in 5,032 live male births. Am. J. Hematol. 59:288–294, 1998. Published 1998 Wiley-Liss, Inc.     

Neuronal activity in the basal ganglia in patients with generalized dystonia and hemiballismus.

Microelectrode recording was performed in the basal ganglia of 3 patients with generalized dystonia and 1 patient with hemiballismus secondary to a brainstem hemorrhage. Neuronal activity was recorded from the internal and external segments of the globus pallidus and assessed for mean discharge rate and pattern of spontaneous activity. The responses of neurons in the internal segment of the globus pallidus to passive and active movements were also evaluated. Mean discharge rates of neurons in both segments of the pallidum in patients with dystonia and the patient with hemiballismus were considerably lower than those reported for patients with idiopathic Parkinson's disease. In addition, the pattern of spontaneous neuronal activity was highly irregular, occurring in intermittent grouped discharges separated by periods of pauses. Although receptive fields in the dystonia patients were widened and less specific than those reported in normal monkeys, neuronal responses to movement were uncommon in the hemiballismus patient. Before surgery, patients with dystonia experienced abnormal posturing and involuntary movements. Coactivation of agonist-antagonist muscle groups was observed both at rest and during the performance of simple movements. After pallidotomy there was a significant reduction in the involuntary movement associated with these disorders and a more normal pattern of electromyographic activity during rest and movement. Given the improvement in dystonic and hemiballistic movements in these patients after ablation of the sensorimotor portion of the internal segment of the globus pallidus, we suggest that pallidotomy can be an effective treatment for patients with dystonia and also for patients with medically intractable hemiballismus. Based on the finding of decreased neuronal discharge rates in pallidal neurons, we propose that physiologically dystonia most closely resembles a hyperkinetic movement disorder. A model for dystonia is proposed that incorporates the observed changes in the rate and pattern of neuronal activity in the pallidum with data from neuroimaging with positron emission tomography and 2-deoxyglucose studies.     

Kinetic study of platelets and fibrinogen in Lassa virus-infected monkeys and early pathologic events in Mopeia virus-infected monkeys

The rhesus monkey, an established model of Lassa fever, was used to study hematologic and hemostatic aspects of Lassa fever and whether Mopeia (also known as Mozambique) virus induces any cellular damage in this model. Six days after subcutaneous injection of 10(3.48) plaque forming units (PFU) of Lassa virus (Josiah strain) one group of monkeys received an intravenous injection of 111In-labeled allogeneic platelets and another group received 125I-labeled alogeneic fibrinogen. Lassa virus-infected monkeys developed a severe clinical illness with high viremia and typical pathology. Lassa antigen was found in most tissues using a Lassa nucleocapsid-specific monoclonal antibody. Platelet counts remained within normal limits. Platelet and fibrinogen kinetics were similar in infected and control animals. Hematologic and hemostatic changes indicate that disseminated intravascular coagulation plays no role in this model of Lassa fever. Levels of plasma fibronectin were reduced in Lassa-infected monkeys. Mopeia virus-infected monkeys were normothemic, aviremic, and there was no detection of Mopeia antigen in any tissues using polyclonal or monoclonal antibodies. Mopeia virus was recovered from the spleen of one monkey. Mopeia virus was associated with hepatocellular and renal tubular damage.     

Use of the polymerase chain reaction to detect hypermethylation in the calcitonin gene. A new, sensitive approach to monitor tumor cells in acute myelogenous leukemia.

Based on the recent observations that, in a majority of patients with acute leukemia, the 5' end of the calcitonin gene was hypermethylated and abnormal DNA fragments were observed following HpaII restriction digestion, we have developed a PCR-based method to sensitively detect this abnormal methylation of the calcitonin gene in AML. Applying the concept of competitive PCR, a semi-quantitative correlation was obtained between the amount of hypermethylation and the amount of leukemic cells present. These results suggest that this method will be useful to monitor the amount of tumor cells in bone marrow from patients with AML.     

Epidemiology of AIDS in females with hemophilia and other chronic bleeding disorders in the United States: comparisons with males with chronic bleeding disorders and AIDS and with nonhemophilic female blood-transfusion recipients with AIDS.

From January 1, 1981 through June 30, 1990, 32 females with chronic bleeding disorders were diagnosed with acquired immunodeficiency syndrome (AIDS) in the United States. Most (81.3%) were white and greater than or equal to 30 years of age, with a median age of 37.5 years. Eighteen (56.3%) had von Willebrand's disease. Pneumocystis carinii pneumonia was reported for 16 (50%). None had Kaposi sarcoma. The median survival time was 10.8 months, with a cumulative probability of survival at 1 year of 47.3% and at 2 years of 27.6%. We compared the demographic data and survival times of these females with those of males with a chronic bleeding disorder and AIDS, and with those of nonhemophilic females with AIDS whose exposure to the human immunodeficiency virus (HIV) was through receipt of blood transfusions, blood components, or tissue. The principal demographic difference was age distribution. The females with chronic bleeding disorders tended to be younger than the transfused, nonhemophilic females, but older than the males. The survival time from AIDS diagnosis to death for the females with chronic bleeding disorders did not differ statistically from that of the other two groups, although older nonhemophilic females whose exposure was transfusion may progress more rapidly to AIDS.