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J M Silverman

Publications and source records attributed to J M Silverman.

At least 55 records · Page 3Linked to original sources
PubMed1996

Apolipoprotein E-epsilon 4 allele and familial risk in Alzheimer's disease.

Recent studies have found an association between presence of apolipoprotein E (APOE) epsilon 4 allele and Alzheimer's disease (AD). The present study compared the cumulative risk of primary progressive dementia (PPD) in relatives of AD probands carrying at least one copy of the epsilon 4 allele with the relatives of AD probands not carrying epsilon 4 and with relatives of non-demented controls. Our aim was to determine whether the familial aggregation of PPD in relatives of AD probands is primarily due to those carrying epsilon 4. Seventy-seven neuropathologically diagnosed AD patients were obtained as probands through our Alzheimer's Disease Research Center Brain Bank. AD probands were genotyped for APOE. As a comparison group, 198 non-demented probands were also included. Through family informants, demographic and diagnostic data were collected on 382 first-degree relatives (age > or = 45 years) of AD probands and 848 relatives of the controls. We found that the cumulative risk of PPD in both relatives of AD probands with and without the epsilon 4 allele was significantly higher than that in the relatives of non-demented controls. However, the increased risk in the relatives of AD probands with the epsilon 4 allele was marginally, but not significantly, lower than the risk in the relatives of probands without epsilon 4. A greater likelihood of death by heart diseases over developing PPD in relatives of AD probands with epsilon 4 (3.1-fold increase) was found compared to relatives of probands without epsilon 4 (1.7-fold increase), especially prior to age 70, although the difference was not statistically significant. The increased familial risk for PPD in the relatives of AD probands with the APOE-epsilon 4 allele relative to controls suggests that familial factors in addition to APOE-epsilon 4 are risk factors for AD. Differential censorship from increased mortality of heart diseases may have prevented a higher incidence of PPD among the relatives of probands with epsilon 4.

Age of Onset↗
PubMed1996

Increased risk of dementia in mothers of Alzheimer's disease cases: evidence for maternal inheritance.

This study tests the hypothesis of maternal inheritance of AD in families of 118 subjects with this disorder enrolled in The Consortium to Establish a Registry for Alzheimer's Disease (CERAD). The parental generation included 24 subjects with dementia. Using the Cox proportional hazards model, we found the age-adjusted mother-to-father relative risk to be 2.8 (95% CI, 1.1 to 7.7). Among a subset of 10 families with one affected parent and at least two affected siblings, the ratio of affected mothers-to-fathers was 9:1. These findings support recent studies that found a high mother-to-father ratio among affected parents of subjects with AD. Together, these results suggest maternal inheritance of AD and are consistent with several hypotheses regarding the genetic nature of AD.

Aged↗
PubMed1996

Detection of main renal artery stenosis using phase-contrast cine MR angiography.

OBJECTIVE: The purpose of our study was to assess the ability of phase-contrast cine MR angiography to detect the presence of main renal artery stenosis. SUBJECTS AND METHODS: We prospectively evaluated 75 hypertensive patients form main renal artery stenosis using phase-contrast cine MR angiography. Each main renal artery was evaluated as normal or abnormal. Thirty-seven of the 75 patients underwent conventional arteriography or intraarterial digital subtraction arteriography; these results were compared with the MR angiographic interpretations. Only those patients who had confirmatory arteriography were included in the statistical analysis. RESULTS: Thirty-six main renal arteries interpreted as normal by MR angiography were found to be without a focal stenosis on invasive arteriography. MR angiography suggested 32 main renal artery stenoses; invasive arteriography showed 29 of these as stenoses. Three main renal arteries that were interpreted as having focal stenoses by MR angiography were shown to be not stenotic by invasive arteriography. Three other patients had diffusely narrowed main renal arteries bilaterally without a focal stenosis on MR angiography; bilateral proximal renal artery stenoses were seen at arteriography in two of these patients, and diffusely narrowed main renal arteries were seen in the third patient. Thus, the sensitivity of phase-contrast cine MR angiography for detecting a focal stenosis or abnormal main renal artery was 100% (95% confidence interval, 88-100%) and the specificity was 93% (95% confidence interval, 80-99%). The kappa coefficient was 0.85 with a standard error of 0.08. CONCLUSION: Phase-contrast cine MR angiography had a high degree of accuracy and a high negative predictive value in detecting the presence of main renal artery stenoses and may be a good screening technique for renovascular hypertension.

Adult↗
PubMed1996

Ventricular enlargement associated with linkage marker for schizophrenia-related disorders in one pedigree.

We previously obtained evidence indicating a genetic linkage marker for schizophrenia and related disorders (two-point lod score = 3.72, P = 0.01) on the short arm of chromosome 5(5p14.1-13.1) in one large pedigree. Automated computer algorithms were used to edge the brain and measure the volume of the ventricles, regional sulcal atrophy, and skull size and shape in the original nuclear family members. Of the 11 subjects who underwent computed tomography, six (three schizophrenic, two with schizotypal personality disorder, and one unaffected) carried the marker allele that co-segregated with schizophrenia-related disorders, while five (all unaffected) did not. The family members with the marker allele linked to schizophrenia-related disorders (n = 6) had significantly (P < 0.05) larger ventricle-brain ratios (VBRs) and more fronto-parietal atrophy (controlling for age) than the family members lacking the schizophrenia-related marker allele (n = 5). The three individuals with the largest VBRs all carried the marker, although they received diagnoses of no schizophrenia-related disorder, schizotypal personality disorder, and schizophrenia. Regional cortical values indicative of cerebrospinal fluid content were higher in the frontal and parietal regions of family members carrying the marker. The hypothesis that genetic linkage is associated with structural brain pathology is difficult to test because of all the potential compounding factors. Our findings suggest the possibility that, in this family, relatively enlarged VBR and fronto-parietal atrophy, as determined by computed tomograph, may be associated with a schizophrenia-related gene and present susceptibility to schizophrenia-related disorders. In addition to a replication of these findings in other similarly linked families yet to be identified, further studies using higher resolution structural and functional neuroimaging techniques will be required.

Brain↗
PubMed1995

Atrial emptying with orthotopic heart transplantation using bicaval and pulmonary venous anastomoses: a magnetic resonance imaging study.

OBJECTIVES: We hypothesized that orthotopic heart transplantation with bicaval and pulmonary venous anastomoses preserves atrial contractility. BACKGROUND: The standard biatrial anastomotic technique of orthotopic heart transplantation causes impaired function and enlargement of the atria. Cine magnetic resonance imaging (MRI) allows assessment of atrial size and function. METHODS: We studied 16 patients who had undergone bicaval (n = 8) or biatrial (n = 8) orthotopic heart transplantation without evidence of rejection and a control group of 6 healthy volunteers. For all three groups, cine MRI was performed by combining coronal and axial gated spin echo and gradient echo cine sequences. Intracardiac volumes were calculated with the Simpson rule. Atrial emptying fraction was defined as the difference between atrial diastolic and systolic volumes, divided by atrial diastolic volume, expressed in percent. All patients had right heart catheterization. RESULTS: Right atrial emptying fraction was significantly higher in the bicaval (mean [+/- SD] 37 +/- 9%) than in the biatrial group (22 +/- 11%, p < 0.05) and similar to that in the control group (48 +/- 4%). Left atrial emptying fraction was significantly higher in the bicaval (30 +/- 5%) than in the biatrial group (15 +/- 4%, p < 0.05) and significantly lower in both transplant groups than in the control group (47 +/- 5%, p < 0.05). The left atrium was larger in the biatrial than in the control group (p < 0.05). Cardiac index, stroke index, heart rate and blood pressure were similar in the transplant groups. CONCLUSIONS: Left and right atrial emptying fractions are significantly depressed with the biatrial technique and markedly improved with the bicaval technique of orthotopic heart transplantation. The beneficial effects of the latter technique on atrial function could improve allograft exercise performance.

Adult↗
PubMed1995

Malignant vascular tumors of the liver presenting as liver failure and portal hypertension.

We describe three patients referred for orthotopic liver transplantation with liver failure and portal hypertension who were found to have malignant vascular tumors: two patients with angiosarcoma and one patient with epithelioid hemangioendothelioma. Their clinical presentation mimicked decompensated chronic liver disease. None had tumor masses on computed tomography and ultrasonography. Massive tumor involvement of the liver was identified in the two patients studied by magnetic resonance imaging. Pathological examination of the explanted liver at the time of transplantation in one patient and autopsy in a second patient showed angiosarcoma. Laparoscopic liver biopsies in the third patient showed epithelioid hemangioendothelioma. The vascular origin of the tumor was established by histopathologic examination and confirmed with immunohistochemistry. Malignant vascular tumors of the liver should be included in the differential diagnosis of liver failure of unclear etiology.

Adult↗
PubMed1995

Portal vein patency in candidates for liver transplantation: MR angiographic analysis.

PURPOSE: To assess the accuracy of magnetic resonance (MR) angiography for evaluating portal vein patency in candidates for liver transplantation. MATERIALS AND METHODS: MR angiography was performed in the main portal vein and proximal confluence of the portal vein in 102 candidates for liver transplantation (64 male patients and 38 female patients aged 8 months to 74 years; mean age, 47 years). The MR angiographic results were compared with the surgical and histologic findings in the explanted liver and excised main portal vein. RESULTS: MR angiography depicted 10 portal vein clots, all of which were confirmed at transplantation. Ninety-two portal veins were patent at MR angiography, a finding that was confirmed at transplantation. One tiny chronic clot in a small, intrahepatic branch of the portal vein was not seen at MR angiography or transplantation. It was identified at histologic analysis of the explanted liver. CONCLUSION: MR angiography is accurate in the evaluation of portal vein patency.

Adolescent↗
PubMed1995

Age at onset and familial risk in Alzheimer's disease.

OBJECTIVE: The authors investigated the relationship between probands' age at onset of Alzheimer's disease with the risk of primary progressive dementia in the probands' first-degree relatives. METHOD: Two hundred probands with clinically diagnosed Alzheimer's disease and 179 nondemented elderly probands were recruited from the Mount Sinai Alzheimer's Disease Research Center, located at Mount Sinai Hospital and the Bronx Veterans Affairs Medical Center. Demographic and diagnostic data were collected on 1,398 of the first-degree relatives of the probands with Alzheimer's disease and 955 first-degree relatives of the nondemented probands. RESULTS: Cox proportional hazards regression analysis showed a significant inverse relationship between age at onset of Alzheimer's disease in probands and greater familial risk in their relatives. Follow-up analyses indicated that the most commonly used age at onset cutoff point--65 years--was one of the points where an association with familial aggregation is least likely to be revealed; other onset cutoff ages (e.g., 55, 70, and 75) better identified Alzheimer's disease groups with differing familial/genetic risks. CONCLUSIONS: The authors conclude that patients with an earlier age at onset of Alzheimer's disease are more likely to have relatives with Alzheimer's disease than are patients with a later age at onset of the disease. An onset age of 70 best differentiated probands whose relatives were at higher risk from those whose relatives were at lower risk.

Age of Onset↗
PubMed1994

Familial correlates of reduced central serotonergic system function in patients with personality disorders.

BACKGROUND: To test the hypothesis that evidence of reduced central serotonergic (5-HT) system function in probands with personality disorders is associated with an elevated morbid risk of psychopathological conditions putatively associated with 5-HT dysfunction in first-degree relatives of these probands. METHODS: Data were collected during a study of the 5-HT correlates of behavior in male patients with DSM-III personality disorders conducted at a Veterans Affairs medical center. Probands in this study were selected from those patients who had undergone both a fenfluramine hydrochloride challenge and a family history assessment. Axis II diagnosis were made according to DSM-III criteria after a structured interview of the proband, using the Structured Interview for Diagnosing Personality Disorders, given by two raters and a similar interview with a knowledgeable informant by another rater. RESULTS: Reduced prolactin responses to the 5-HT releasing/uptake inhibiting agent fenfluramine was associated with an elevated morbid risk of impulsive personality disorder traits in the first-degree relatives of patients with a primary DSM-III diagnosis of a personality disorder. Quantitative scores on assessments of impulsive aggression in the probands were not correlated with an increased morbid risk for impulsive personality disorder traits. A trend in the same direction was noted for affective personality disorder traits and alcoholism. CONCLUSIONS: These results suggest that a central 5-HT system abnormality in probands is associated with an increased risk of impulsive aggression in their first-degree relatives, and that assessment of central 5-HT system function in probands may be a more sensitive parameter for identification of this familial trait than the presence of impulsive aggressive behaviors in the proband.

Aggression↗
PubMed1994

Patterns of risk in first-degree relatives of patients with Alzheimer's disease.

BACKGROUND: Although an increased cumulative risk for primary progressive dementia (PPD) has been repeatedly demonstrated in relatives of probands with Alzheimer's disease (AD), an examination of their rates of illness at different ages has not been previously undertaken. Such an examination might reveal possible age-related characteristics associated with a more familial variety of AD. METHODS: Using family history interviews and survival analysis, the cumulative risk for and 5-year age-specific hazard rates of PPD were assessed in the first-degree relatives of 200 probands with AD and two nondemented control groups--179 elderly ascertained through the Alzheimer's Disease Research Center (ADRC-derived controls) and 427 elderly ascertained from community senior centers (community controls). RESULTS: The PPD risk curve for the relatives of probands with AD rose to about 30% and was significantly higher than the curves for the relatives of the ADRC-derived and community controls, where comparable rates were observed (approximately 12%). The age-specific hazard rates of PPD were calculated in three groups of relatives for each 5-year interval from ages 45 to 49 years through ages 85 to 89 years. The age-specific relative risk (RRi) for PPD in the relatives of probands with AD began to steadily diminish from the 75- to 79-year age interval (RRi = 13.49) through the 85- to 89-year age interval (RRi = 0.96) compared with the relatives of ADRC-derived controls and from the 60- to 64-year age interval (RRi = 16.15) through the 85- to 89-year age interval (RRi = 2.03) compared with the relatives of the community controls. CONCLUSIONS: These data indicate that, for relatives of probands with AD, while the lifetime risk for PPD is greater than in relatives of controls, the familial contribution to the risk for PPD decreases with increasing age. The higher risk for PPD in relatives of probands with AD may be substantially diminished or even eliminated by the latter half of the ninth decade.

Age Factors↗
PubMed1994

Performance of nonpsychotic relatives of schizophrenic patients on cognitive tests.

We tested 54 nonpsychotic first degree relatives of 23 schizophrenic probands and 18 control subjects matched for age and education on several neuropsychological tests. The tests were selected to assess overall intellectual ability or because previous work indicated that they are particularly sensitive measures of cognitive dysfunction in schizophrenic patients. The relatives of schizophrenic patients performed significantly worse than the control subjects on tests of verbal fluency and on Trailmaking, part B. Each of these tests contributed unique variance to the discrimination between groups. The groups did not differ significantly on the number of perseverative errors on the Wisconsin Card Sorting Test, Wechsler Adult Intelligence Scale-Revised block design or vocabulary, or Trailmaking, part A. Eight relatives who met DSM-III-R criteria for schizotypal personality disorder were more impaired than the remaining 46 relatives on letter fluency, but otherwise their performance was similar to that of nonschizotypal relatives. These data suggest that close relatives of schizophrenic patients may have subtle neuropsychological impairments that are not necessarily associated with clinical symptoms of schizophrenia spectrum disorders.

Adult↗
PubMed1994

The Consortium to Establish a Registry for Alzheimer's Disease (CERAD). Part VI. Family history assessment: a multicenter study of first-degree relatives of Alzheimer's disease probands and nondemented spouse controls.

Although familial factors in Alzheimer's disease (AD) are well established, uniform family-history assessment in genetic and epidemiologic studies of AD is needed to reconcile the divergent estimates of the cumulative risk of this illness among relatives of AD probands. To answer the need, the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) has developed a standardized Family History Assessment of AD to identify the presence of AD, Parkinson's disease (PD), and Down's syndrome (DS) in family members. This paper describes the use of this new assessment instrument in 118 patients with AD (estimated mean age at onset [+/- SD] = 64.5 +/- 7.7 years) and their nondemented spouses who were enrolled in 11 different CERAD sites in the U.S. The first-degree relatives of the probands with AD had a significantly greater cumulative risk (p < 0.005) of AD or primary progressive dementia (24.8%) than did the relatives of spouse controls (15.2%). Furthermore, the cumulative risk for this disorder among female relatives of probands was significantly greater than that among male relatives. There were no differences between the families of probands and controls for the numbers of affected first-degree relatives with PD or DS. This is the first reported multicenter family-history study of AD, and it supports earlier reports of familial factors in AD and indicates a higher risk to female relatives of AD probands. The CERAD Family History Assessment instrument may be useful for further multicenter and epidemiologic studies designed to delineate familial factors associated with AD.

Age of Onset↗
PubMed1994

Magnetic resonance imaging evaluation of pulmonary vascular malformations.

OBJECTIVE: The purpose of our study was to establish magnetic resonance imaging (MRI) criteria for the diagnosis of pulmonary vascular malformations (PVMs). MATERIALS AND METHODS: Since 1987, 11 patients have been referred for chest MRI at our institution because of findings suggestive of a PVM. They were evaluated with a 1.5-T MRI system, incorporating a combination of spin-echo, gradient-recalled echo (GRE) cine, and 2-D phase contrast (PC) cine sequences. We used the following MRI criteria to diagnose PVM: (1) flow void or intermediate gray signal on spine-echo sequences; (2) bright signal on GRE cine sequences; and (3) bright signal consistent with flow detected on PC cine sequences using relatively low velocity ranges. Twelve patients not suspected of having a PVM served as controls; all had both MRI and pulmonary angiography to evaluate for central pulmonary embolus. RESULTS: Eight patients in the study group had PVM as determined with MRI using these criteria. In four of these patients, a PVM was confirmed by subsequent pulmonary angiography. Three patients did not have PVM utilizing these criteria; two had neoplasms and one had presumed mucus plugging and/or atelectasis that resolved spontaneously. The smallest vascular malformation detected by MRI was 1 cm. None of the control patients had PVM by MRI or pulmonary angiography. CONCLUSION: Utilizing these criteria, we believe that MRI is potentially an excellent noninvasive modality to evaluate PVM, and we stress that some form of PC cine sequence must be performed to determine if indeed there is blood flow within a suspicious lesion.

Adolescent↗
PubMed1994

Pretreatment with corticosteroids to prevent adverse reactions to nonionic contrast media.

OBJECTIVE: The purpose of this study was to determine whether patients receiving a two-dose corticosteroid regimen before IV injection of nonionic contrast medium gain protection against adverse reactions to contrast material. SUBJECTS AND METHODS: A randomized, blinded study involving three institutions was initiated in 1988. Patients were divided into two groups. One group received a 32-mg oral dose of methylprednisolone administered 6-24 hr before and again 2 hr before injection of contrast material. The other group received placebo tablets administered in the same time periods. During a 3-year period, 1155 patients and control subjects successfully completed the protocol. Demographic characteristics, including histories of previous reactions and histories of asthma or allergy, did not differ in the two groups. All signs and symptoms that appeared after injection of contrast material were carefully recorded and graded according to an earlier scheme [1]. Patients, control subjects, and all attending personnel were blinded regarding the premedication. RESULTS: Corticosteroid pretreatment conferred protection for overall reactions (1.7% vs 4.9%, p = .005) and grade I (mild) reactions (0.2% vs 1.9%, p = .004). Subjects receiving corticosteroids also had fewer grade II (moderate) (p = .63) and grade III (severe) (p = .11) reactions, but the total numbers involved were small, and the differences were not significant. CONCLUSION: A rigidly controlled study of the potential protective effects of a two-dose oral corticosteroid regimen preceding IV injection of nonionic contrast medium indicates that corticosteroid pretreatment confers significant protection, at least for overall reactions and grade I reactions.

Administration, Oral↗
PubMed1993

Use of laser energy to treat central pulmonary emboli: a preliminary report.

We evaluated the ability and safety of a laser fiber placed percutaneously into a pig's lobar pulmonary artery to lyse pulmonary artery blood clots that were created in situ. We developed a model to create blood clots in situ that could be placed in any desired location with a radio-opaque marker at the clot position. An excimer laser delivered energy to a flexible 600 microns fiber in three experiments and a coaxial 1.6 mm multifiber catheter in the last experiment. Pre- and postprocedure angiograms obtained from each experiment demonstrated that partial laser dissolution of central pulmonary emboli in four pigs was accomplished successfully. To avoid perforation, it is imperative that the laser fiber remain coaxial during the entire lasing process. These results suggest that laser dissolution may become an adjunctive procedure for the treatment of central pulmonary emboli in those patients who cannot be treated medically.

Animals↗
PubMed1993

Quantitative differential pulmonary perfusion: MR imaging versus radionuclide lung scanning.

PURPOSE: To compare the results of quantitative analysis of differential pulmonary artery blood flow performed with phase-contrast cine magnetic resonance (MR) images with those of differential radionuclide pulmonary perfusion scanning in preoperative lung transplantation patients. MATERIALS AND METHODS: Forty preoperative lung transplantation patients underwent prospective, quantitative analysis of differential pulmonary artery blood flow performed with MR imaging and radionuclide pulmonary perfusion scanning. MR imaging analysis was performed at 1.5 T with a phase-contrast cine pulse sequence to acquire data perpendicular to each central pulmonary artery. RESULTS: Comparative analysis of differential pulmonary perfusion showed excellent correlation between the two modalities in all patients (P = .0001). MR imaging enabled calculation of the pulmonary artery blood flow to each lung; radionuclide lung scanning enabled only calculation of relative perfusion to each lung. CONCLUSION: MR imaging is as effective as radionuclide lung scanning in assessment of relative, and superior for determination of absolute differential, pulmonary perfusion.

Humans↗
PubMed1993

Schizophrenia-related and affective personality disorder traits in relatives of probands with schizophrenia and personality disorders.

OBJECTIVE: The possible heterogeneity of the schizophrenia-related personality disorder traits associated with DSM-III criteria for schizotypal personality disorder was investigated using the family history method. A familial relationship to schizophrenia was hypothesized for schizophrenia-related personality disorder traits without coexisting affective personality disorder traits, pure schizophrenia-related personality disorder traits. Alternatively, a familial relationship with borderline personality disorder was hypothesized for schizophrenia-related personality disorder traits with comorbid affective personality disorder traits. METHOD: Criteria for schizophrenia-related and affective personality disorder traits were used to assess the 588 nonpsychotic first-degree relatives of 55 chronic schizophrenic probands and 67 probands with personality disorders. The probands with one or more DSM-III personality disorders were categorized as having schizotypal personality disorder without borderline personality disorder (pure schizotypal personality disorder), borderline personality disorder without schizotypal personality disorder (pure borderline personality disorder), both disorders, or neither. RESULTS: The morbid risk of all cases of schizophrenia-related personality disorder traits was higher in relatives of probands with schizophrenia and pure schizotypal personality disorder than in relatives of probands with neither schizotypal nor borderline personality disorder; however, it differed only slightly from that observed in the relatives of probands with both schizotypal and borderline personality disorders and pure borderline personality disorder. In contrast, the risk of pure schizophrenia-related personality disorder traits was higher in relatives of probands with schizophrenia and pure schizotypal personality disorder, while the risk of coexisting schizophrenia-related and affective personality disorder traits was lower in both of these groups than among the relatives of probands with both schizotypal and borderline personality disorders and pure borderline personality disorder. CONCLUSIONS: These results offer preliminary indications that schizotypal personality disorder features present without comorbid affective personality disorder traits may more specifically characterize the personality characteristics familially related to schizophrenia. Furthermore, they indicate that schizotypal personality disorder features as currently defined are found in relatives of patients other than those with schizophrenia or schizotypal personality disorder.

Adult↗