James Godbold

A Double-blind Controlled Trial of Bilateral Fetal Nigral Transplantation in Parkinson's Disease

Thirty‐four patients with advanced Parkinsons disease participated in a prospective 24‐month double‐blind, placebo‐controlled trial of fetal nigral transplantation. Patients were randomized to receive bilateral transplantation with one or four donors per side or a placebo procedure. The primary end point was change between baseline and final visits in motor component of the Unified Parkinsons Disease Rating Scale in the practically defined off state. There was no significant overall treatment effect (p = 0.244). Patients in the placebo and one‐donor groups deteriorated by 9.4 ± 4.25 and 3.5 ± 4.23 points, respectively, whereas those in the four‐donor group improved by 0.72 ± 4.05 points. Pairwise comparisons were not significant, although the four‐donor versus placebo groups yielded a p value of 0.096. Stratification based on disease severity showed a treatment effect in milder patients (p = 0.006). Striatal fluorodopa uptake was significantly increased after transplantation in both groups and robust survival of dopamine neurons was observed at postmortem examination. Fifty‐six percent of transplanted patients developed dyskinesia that persisted after overnight withdrawal of dopaminergic medication (“off”‐medication dyskinesia). Fetal nigral transplantation currently cannot be recommended as a therapy for PD based on these results.Ann Neurol 2003;54:403–414

US prevalence of self-reported peanut, tree nut, and sesame allergy: 11-year follow-up

BACKGROUND Allergy to peanuts and tree nuts (TNs) is the leading cause of fatal allergic reactions in the United States, and the prevalence appears to be increasing. OBJECTIVES We sought to determine the US prevalence of self-reported peanut, TN, and sesame allergy in 2008 and compare results with comparable surveys conducted in 1997 and 2002. METHODS A nationwide, cross-sectional, random telephone survey for peanut and TN allergy was conducted with a previously used questionnaire, with additional questions about sesame. RESULTS A total of 5,300 households (13,534 subjects) were surveyed (participation rate, 42% vs 52% in 2002 and 67% in 1997). Peanut allergy, TN allergy, or both was reported by 1.4% of subjects (95% CI, 1.2% to 1.6%) compared with 1.2% in 2002 and 1.4% in 1997. For adults, the prevalence was 1.3% (95% CI, 1.1% to 1.6%), which was not significantly different from prior surveys. However, the prevalence of peanut or TN allergy for children younger than 18 years was 2.1% (95% CI, 1.6% to 2.7%) compared with 1.2% in 2002 (P = .007) and 0.6% in 1997 (P < .001). The prevalence of peanut allergy in children in 2008 was 1.4% (95% CI, 1.0% to 1.9%) compared with 0.8% in 2002 (P = not significant) and 0.4% in 1997 (P < .0001). The prevalence of childhood TN allergy increased significantly across the survey waves (1.1% in 2008, 0.5% in 2002, and 0.2% in 1997). Sesame allergy was reported by 0.1% (95% CI, 0.0% to 0.2%). CONCLUSIONS Although caution is required in comparing surveys, peanut allergy, TN allergy, or both continue to be reported by more than 1% of the US population (eg, >3 million subjects) and appear to be increasingly reported among children over the past decade. Sesame allergy is reported much less commonly.

Volume of ventricular blood is an important determinant of outcome in supratentorial intracerebral hemorrhage.

OBJECTIVE To determine the prognostic significance and pathophysiologic implication of intraventricular extension of supratentorial intracerebral hemorrhage. DESIGN Prospective study. SETTING Acute stroke and neurointensive care units of a tertiary care hospital. PATIENTS One hundred twenty-nine patients with supratentorial intracerebral hemorrhage, managed medically. INTERVENTIONS Two patients had intraventricular catheters placed for external drainage. No patient received thrombolytics or surgical evacuation of clot. MEASUREMENTS AND MAIN RESULTS Of the 129 patients, 47 had intraventricular extension of their hemorrhages. These patients had larger intraparenchymal hemorrhages (36.6 cm3 vs. 15.0 cm3) and lower initial Glasgow Coma Scale scores (mean, 9.6 vs. 13.7). Their 30-day mortality rate was 43% compared with only 9% among those without ventricular extension. Univariate and multivariate logistic regression modeling was used to assess the prognostic significance of various measures of intraventricular hemorrhage. The presence of intraventricular hemorrhage, the number of ventricles containing blood, fourth ventricular blood, and intraventricular hemorrhage volume were each related to 30-day mortality in a univariate analysis, but only intraventricular hemorrhage volume contributed significantly to outcome prediction in the presence of Glasgow Coma Scale score. CONCLUSIONS Volume of intraventricular hemorrhage is an important determinant of outcome in supratentorial intracerebral hemorrhage.

Morbidity and mortality in common variable immune deficiency over 4 decades

The demographics, immunologic parameters, medical complications, and mortality statistics from 473 subjects with common variable immune deficiency followed over 4 decades in New York were analyzed. Median immunoglobulin levels were IgG, 246 mg/dL; IgA, 8 mg/dL; and IgM, 21 mg/dL; 22.6% had an IgG less than 100 mg/dL. Males were diagnosed earlier (median age, 30 years) than females (median age, 33.5 years; P = .004). Ninety-four percent of patients had a history of infections; 68% also had noninfectious complications: hematologic or organ-specific autoimmunity, 28.6%; chronic lung disease, 28.5%; bronchiectasis, 11.2%; gastrointestinal inflammatory disease, 15.4%; malabsorption, 5.9%; granulomatous disease, 9.7%; liver diseases and hepatitis, 9.1%; lymphoma, 8.2%; or other cancers, 7.0%. Females had higher baseline serum IgM (P = .009) and were more likely to develop lymphoma (P = .04); 19.6% of patients died, a significantly shorter survival than age- and sex-matched population controls (P < .0001). Reduced survival was associated with age at diagnosis, lower baseline IgG, higher IgM, and fewer peripheral B cells. The risk of death was 11 times higher for patients with noninfectious complications (hazard ratio = 10.95; P < .0001). Mortality was associated with lymphoma, any form of hepatitis, functional or structural lung impairment, and gastrointestinal disease with or without malabsorption, but not with bronchiectasis, autoimmunity, other cancers, granulomatous disease, or previous splenectomy.

Localized extremity soft tissue sarcoma: an analysis of factors affecting survival.

The management of extremity soft tissue sarcoma is undergoing rapid change as new techniques of adjuvant treatment are developed. Critical assessment of these advances requires a fundamental understanding of the natural course of this disease. In an effort to define important prognostic factors, this review of 423 adults with localized extremity soft tissue sarcomas, treated at one institution (1968 to 1978), was undertaken. The effect of the following variables on survival was examined: patient factors, ie, age, sex, symptoms, and status at presentation; tumor factors, ie, site, size, depth, bone or neurovascular invasion, histogenesis, grade, and nodal status; and treatment factors, ie, biopsy technique, type of operation, surgical margins, adjuvant treatment, and subsequent local treatment failure. Patient factors with an adverse impact on survival included age greater than 53 and the presence of local symptoms. High tumor grade, positive regional nodes, histology other than liposarcoma, fibrosarcoma or malignant fibrohistiocytoma, invasion of vital structures, proximal site, deep location, and size greater than 10 cm were also poor prognosticators. Treatment factors correlating with optimal survival included limb sparing surgery, adequate margins, biopsy with delayed definitive resection, and absence of subsequent local failure. Patients treated by amputation had a greater proportion of risk factors than patients treated with limb-sparing surgery (LSS). When the data were subjected to multivariate analysis, the following variables emerged as independent predictors of poor outcome: local symptoms, age greater than 53, high grade, proximal site, size greater than 10 cm, positive regional nodes, surgery by amputation, and inadequate margins. These factors are now to be evaluated in our prospective study based on 600 patients with soft tissue sarcoma of all sites admitted to our institution in the last 3 years. These factors should be considered as important stratifications in prospective trials.

Use of placebo surgery in controlled trials of a cellular-based therapy for Parkinson's disease.

Surgical procedures are frequently introduced into general practice on the basis of uncontrolled studies that are less rigorous than those required for the approval of medical interventions.1 The s...

Dietary baked egg accelerates resolution of egg allergy in children

BACKGROUND Baked egg is tolerated by a majority of egg-allergic children. OBJECTIVE To characterize immunologic changes associated with ingestion of baked egg and evaluate the role that baked egg diets play in the development of tolerance to regular egg. METHODS Egg-allergic subjects who tolerated baked egg challenge incorporated baked egg into their diet. Immunologic parameters were measured at follow-up visits. A comparison group strictly avoiding egg was used to evaluate the natural history of the development of tolerance. RESULTS Of the 79 subjects in the intent-to-treat group followed for a median of 37.8 months, 89% now tolerate baked egg and 53% now tolerate regular egg. Of 23 initially baked egg-reactive subjects, 14 (61%) subsequently tolerated baked egg and 6 (26%) now tolerate regular egg. Within the initially baked egg-reactive group, subjects with persistent reactivity to baked egg had higher median baseline egg white (EW)-specific IgE levels (13.5 kU(A)/L) than those who subsequently tolerated baked egg (4.4 kU(A)/L; P= .04) and regular egg (3.1 kU(A)/L; P= .05). In subjects ingesting baked egg, EW-induced skin prick test wheal diameter and EW-, ovalbumin-, and ovomucoid-specific IgE levels decreased significantly, while ovalbumin- and ovomucoid-specific IgG(4) levels increased significantly. Subjects in the per-protocol group were 14.6 times more likely than subjects in the comparison group (P< .0001) to develop regular egg tolerance, and they developed tolerance earlier (median 50.0 vs 78.7 months; P< .0001). CONCLUSION Initiation of a baked egg diet accelerates the development of regular egg tolerance compared with strict avoidance. Higher serum EW-specific IgE level is associated with persistent baked and regular egg reactivity, while initial baked egg reactivity is not.

Patients at risk for AIDS-related opportunistic infections: clinical manifestations and impaired gamma interferon production.

We studied 81 men (79 homosexuals and 2 drug abusers) with persistent lymphadenopathy to determine whether those at risk for AIDS-related opportunistic infections could be identified prospectively. (Sixty-nine of 76 [91 per cent] had antibodies to human T-cell lymphotropic virus Type III [HTLV-III], and 76 of 79 [96 per cent] had abnormal T4/T8 cell ratios.) During the follow-up period (mean +/- S.E.M., 12.9 +/- 0.5 months; range, 8 to 19), infections developed in none of 38 patients with lymphadenopathy alone and in only 1 of 15 (7 per cent) with antecedent herpes zoster infection; however, 13 of 28 (46 per cent) with lymphadenopathy accompanied by constitutional symptoms or oral candidiasis or both had opportunistic infections within the follow-up period. Among the results of various T-cell assays, only antigen-stimulated lymphocyte proliferation and gamma interferon generation, which were absent or barely measurable in those in whom AIDS ultimately developed, were of prognostic value. T cells from 15 patients, 11 of whom had constitutional symptoms or thrush, failed to generate antigen-induced gamma interferon; infections developed in 10 of these 15 (67 per cent) within a mean of 8.2 months. These results suggest that patients with AIDS-related complex who are at risk for opportunistic infections within a year can be identified by correlating clinical manifestations with antigen-stimulated T-cell responses--in particular, with the production of gamma interferon.

Sleepiness in Parkinson's disease: a controlled study.

Sudden‐onset sleep episodes while driving have been reported in Parkinsons disease (PD) patients, and termed sleep attacks because they were reported to be irresistible and to occur without warning. We postulate that these episodes are due to excessive daytime sleepiness secondary to the high frequency of sleep disorders in PD patients and the sedative effects of dopaminergic medications. We assessed the frequency and relationship between excess daytime sleepiness and sleep episodes while driving (SE) in patients with PD. We evaluated 101 consecutive PD patients presenting to the Movement Disorder Center at the Mount Sinai School of Medicine using a questionnaire that incorporated a subjective estimate of sleepiness, the Epworth Sleepiness Scale (ESS) and information on disease severity and dopaminergic medications. One hundred age‐matched respondents without PD served as a control population. Excess daytime sleepiness was reported in 76% of PD patients compared to 47% of controls (P < 0.05). The mean ESS scores for PD patients was 9.1 ± 6.1 versus 5.7 ± 4.4 in controls (P < 0.001). ESS scores ≥10 were observed in 40.6% of PD patients compared to 19% of controls (P < 0.01) and 24% of PD patients had scores ≥15, compared to 5% of controls (P < 0.001). Sleep episodes while driving were experienced by 20.8% of PD drivers compared to 6% of control drivers (P < 0.05). The mean daily levodopa (L‐dopa) dose equivalent was 1,142 ± 858 mg in PD drivers who experienced a SE while driving compared to 626 ± 667 mg in those who had not (P < 0.05). Similarly, ESS was significantly greater in drivers with a SE than in those without (11.6 ± 6.4 vs. 8.4 ± 4.1; P < 0.05). Logistic regression analysis demonstrated that ESS and mean daily L‐dopa dose equivalents were predictors of sleep episodes while driving, whereas age, gender, disease severity, and individual dopaminergic agents were not. These findings support the notion that sleep episodes while driving in PD patients are related to excess daytime sleepiness and dopaminergic load. Physicians should advise and treat patients accordingly.

Race and food store availability in an inner-city neighbourhood

BACKGROUND A growing body of research has shown that disparities in resources, including food stores, exist at the neighbourhood level and the greatest disparities are seen in minority neighbourhoods, the same neighbourhoods at increased risk of obesity and diabetes. Less is known about whether differences in availability of resources by African American or Latino race/ethnicity exist within a single minority community. OBJECTIVE The present study examined whether census blocks either 75% African American (AA) or 75% Latino (L) are associated with food store availability, as compared with racially mixed (RM) census blocks, in East Harlem, New York. DESIGN/METHODS A cross-sectional study utilising a walking survey of East Harlem was performed. Food stores were classified into: supermarkets, grocery stores, convenience stores, specialty stores, full-service restaurants and fast-food stores. RESULTS One hundred and sixty-five East Harlem census blocks were examined; 17 were AA, 34 were L and 114 were RM. Of AA census blocks, 100% had neither supermarkets nor grocery stores. AA census blocks were less likely to have convenience stores (prevalence ratio (PR) = 0.25, 95% confidence interval (CI) 0.07-0.86) compared with RM census blocks. In contrast, predominantly L census blocks were more likely to have convenience stores (PR = 1.8, 95% CI 1.20-2.70), specialty food stores (PR = 3.74, 95% CI 2.06-7.15), full-service restaurants (PR = 1.87, 95% CI 1.04-3.38) and fast-food restaurants (PR = 2.14, 95% CI 1.33-3.44) compared with RM census blocks. CONCLUSIONS We found that inequities in food store availability exist by race/ethnicity in East Harlem, New York. This has implications for racial/ethnic differences in dietary quality, obesity and obesity-related disorders.