Martin Lesser

Commitment to X Inactivation Precedes the Twinning Event in Monochorionic MZ Twins

To gain insight into the timing of twinning, we have examined a closely related event, X-chromosome inactivation, in female MZ twin pairs. X-inactivation patterns in peripheral blood and buccal mucosa were compared between monochorionic MZ (MC-MZ) and dichorionic MZ (DC-MZ) twins. Overall, the MC-MZ twins displayed highly similar X-inactivation patterns, whereas DC-MZ twins frequently differed in their X-inactivation patterns, when both tissues were tested. Previous experimental data suggest that commitment to X inactivation occurs when there are 10-20 cells in the embryo. Simulation of embryo splitting after commitment to X inactivation suggests that MC-MZ twinning occurs three or four rounds of replication after X inactivation, whereas a DC-MZ twinning event occurs earlier, before or around the time of X inactivation. Finally, the overall degree of skewing in the MZ twins was not significantly different from that observed in singletons. This indicates that X inactivation does not play a direct role in the twinning process, and it further suggests that extreme unequal splitting is not a common mechanism of twin formation.

Prediction of fetal macrosomia using sonographically measured abdominal subcutaneous tissue thickness

We assessed the usefulness of sonographic measurement of abdominal subcutaneous tissue thickness in predicting fetal macrosomia (weight > 4,000 g).

Neuropsychological Testing in Adult Attention Deficit Hyperactivity Disorder: A Pilot Study

Diagnosing adult ADHD is frequently problematic because behavioral information from the patients childhood, and multiple informants who can delineate the patients current behavior, are often unavailable. This preliminary study was designed to explore whether objective neuropsychological testing may be a useful adjunct in the diagnosis of adult ADHD. Nineteen adults diagnosed with ADHD according to DSM-IV criteria, along with 10 controls, were assessed using a neuropsychological battery which comprised tests assessing linguistic, visual-spatial perceptual, academic, attentional and inhibitory control, mnestic and executive functions. Following preliminary analyses, designed to determine which variables best discriminated the groups, receiver operating characteristic (ROC) curves were constructed to determine the sensitivity and specificity of the best measures both alone and in combination. Only three measures significantly (p < 0.01) distinguished the groups; Digits Backwards from the WAIS-R and two reaction time measures from a computerized task modeled after Lurias Competing Motor Programs. ROC curve analyses indicated that in combination these measures had greater than 90% accuracy for classifying ADHD and non-ADHD patients. While further research is necessary these preliminary findings suggest that neuropsychological testing may be a useful adjunct in the differential diagnosis of adult ADHD.

Modulation by DLST of the genetic risk of Alzheimer's disease in a very elderly population

The mitochondrial α‐ketoglutarate dehydrogenase complex (KGDHC) is deficient in Alzheimers disease (AD). The DLST gene encodes the core, dihydrolipoyl succinyltransferase (DLST) component of KGDHC, and recent reports indicate an association between polymorphisms of DLST and AD in both white and Japanese patients. We therefore examined the relationship between AD and the DLST and apolipoprotein E (APOE) genes in elderly (89 ± 7 years) AD patients, in whom the ε4 allele of APOE (APOE4) is a weak risk factor for AD. Polymorphisms of DLST (A19,117G and T19,183C), shown to be of interest in previous studies, were analyzed by restriction fragment length polymorphism analysis after polymerase chain reaction amplification. In a series of 429 white subjects from two Jewish nursing homes, an association of APOE4 with AD was found only in patients homozygous for the G,C allele of DLST. Similar relationships occurred in the “very elderly” (≥85 years, n = 302) subgroup of this series, and also in an autopsy series (n = 225) that included white subjects from the Jewish nursing homes as well as other white subjects. These findings suggest a relationship between APOE4 and a DLST locus in the pathogenesis of AD in very elderly subjects. Ann Neurol 1999;45:48–53

Anticipation in Crohn's disease may be influenced by gender and ethnicity of the transmitting parent

Objective:We sought to examine whether anticipation (an earlier age of onset in succeeding generations) is observed in Crohns disease (CD) patients within the New York metropolitan area, and whether there are differences in the degree of anticipation with respect to gender and ethnicity of the affected parent.Methods:Sixty-one parent-child pairs both affected by CD were identified; about half of the pairs were of Ashkenazi Jewish descent. An additional 17 pairs of second-degree relatives with CD were also identified. The intergenerational difference in age at diagnosis (AAD) was used to perform regression analysis and the degree of anticipation among subsets of patients separated on the basis of gender and ethnicity of the transmitting parent was determined.Results:The AAD was consistently (90% of the time) lower in the younger member of the 61 parent-child pairs (35.3 ± 1.6 yr vs 20.8 ± 1.1 yr, p= 0.0001). Furthermore, the degree of anticipation was significantly greater for father-child pairs (20.6 ± 3.2 yr) than for mother-child pairs (11.7 ± 2.1 yr). However, when the patient population where the parent had an AAD of < 28 was analyzed separately, there was a lack of clear-cut evidence of anticipation in the population as a whole. Only when the population was subdivided by ethnicity was there convincing evidence of anticipation in the Jewish population.Conclusions:Ascertainment bias may be responsible for the apparent anticipation observed in the CD population as a whole or in the nonJewish CD subgroup. However, the Jewish CD population displays strong evidence of anticipation even after correction for ascertainment bias.

Impact of Spiral Computed Tomography on the Diagnosis of Pulmonary Embolism in a Community Hospital Setting

Background: While the optimal role of spiral CT angiography (CTA) in the diagnosis of pulmonary embolism (PE) remains controversial, this technology is already being widely utilized in the community setting. Objectives: To assess the impact CTA has had on angiography utilization rates and the overall diagnostic rate of PE. Methods: All patients evaluated for PE during a 4-year period were studied. PE was defined as either a high-probability V/Q scan, a positive conventional angiogram, or a CTA with emboli in the segmental or larger pulmonary vessels. Diagnostic rates of PE per 1,000 hospital admissions were determined and analyzed for time periods before and after the introduction of CTA. CT reports were compared with their concurrent chest radiograph (CXR) reports and additional findings that were not apparent on CXR were abstracted. Results: The diagnostic rate of PE per 1,000 hospital admissions was 1.8 prior to the introduction of CTA and increased to 2.8 per 1,000 admissions after the introduction of CTA (p < 0.0001). Total costs for diagnostic testing per PE diagnosis made went from

Is chemiluminescent immunoassay an appropriate substitution for radioimmunoassay in monitoring estradiol levels

2,518 to

Opioids prolong nuclear hepatobiliary imaging when given prior to scanning

2,572. While the number of PE diagnosed by V/Q scan remained constant, the number of PE diagnosed by conventional angiography decreased while the number diagnosed by CTA increased. In patients with intermediate probability V/Q scan results, the percentage of patients receiving subsequent angiography (conventional or CTA) increased from 17 to 26% (p = 0.043). When conventional angiography was performed, CT imaging of the chest still had to be ordered for other reasons 38% of the time. Additional information was obtained in 78% of cases when CTA was performed. Conclusions: Increased utilization of CTA was associated with an increase in angiography utilization rates and diagnostic rates of PE, was cost effective, and often provided additional, useful, and unanticipated diagnostic information.

Admission C-reactive protein does not predict functional outcomes in patients with strokes in a subacute rehabilitation unit.

OBJECTIVEnTo determine the correlation between serum estradiol measurements by chemiluminescent immunoassay (CIA) vs. radioimmunoassay (RIA) in two groups: patients treated with gonadotropins and patients treated with oral estrogen.nnnDESIGNnProspective study.nnnSETTINGnAssisted Reproductive Technology (ART) program based in a university-affiliated hospital in Manhasset, New York.nnnPATIENT(S)nThree hundred forty-eight patients undergoing gonadotropin stimulation and 63 patients receiving oral estrogen between July and December, 1997.nnnINTERVENTION(S)nEstradiol levels were measured concomitantly on all patients undergoing gonadotropin stimulation for IVF and all patients receiving oral estrogen for a frozen-thaw cycle.nnnMAIN OUTCOME MEASURE(S)nRIA:CIA ratio.nnnRESULT(S)nIn the group undergoing gonadotropin stimulation, the median RIA:CIA ratio was 0.92, RIA = 1.26 x CIA(0.96), r = 0.98. In the group receiving oral estrogen, the median ratio was 3.93, RIA = 2.9 x CIA(1.05), r = 0.89.nnnCONCLUSION(S)nEstradiol levels determined by CIA correlate closely with RIA results for patients being treated with gonadotropins. Conversely, for patients receiving oral estrogen, CIA levels are one-third or less of the RIA level.

The Utility of Quantitative Body Surface Isoarea Mapping for Predicting Ventricular Tachyarrhythmias

Opioid-mediated contraction of the distal common bile duct (CBD) may delay tracer passage during nuclear hepatobiliary imaging (NHI), mimicking pathologic obstruction. We sought to determine if opioid administration before NHI delays CBD visualization and prolongs imaging. The records of 198 Emergency Department patients who underwent NHI were reviewed (after excluding those with evidence for pathologic CBD obstruction). Opioids were administered before NHI in 56 cases. Delayed CBD visualization occurred in 28.6% of subjects who had received opioids and in 12.0% of those who had not (p < 0.01). Delayed imaging was performed in 77.8% of those who had received opioids and in 53.5% of those who had not (p < 0.01). The relative risk of delayed CBD visualization was 1.46 [95%CI 0.65-3.28] for meperidine, 4.18 [95%CI 2.00-8.82] for morphine, and 2.38 [95%CI 1.29-4.39] for any opioid. We conclude that opioids given before NHI are associated with delayed CBD visualization and more imaging sessions.