Showing papers by "Jewish Hospital published in 1990"

Dual energy radiography versus quantitative computer tomography for the diagnosis of osteoporosis.

Abstract: In this study we compared dual energy radiography (DER), a new, highly precise x-ray densitometric technique recently devised for measurements of vertebral mineral density and quantitative computer tomography (QCT), a densitometric technique that selectively measures the trabecular compartment of the vertebra. DER and QCT measurements were obtained in 56 healthy (H) and 48 fractured osteoporotic (OP) women using a Hologic QDR 1000 bone densitometer and a GE 9800 scanner, respectively. DER was significantly correlated with QCT in both the H (r = 0.75; P less than 0.0001) and the OP subjects (r = 0.58; P less than 0.0001). DER decreased significantly with age in the H (P less than 0.05), but not in the OP women, whereas QCT was related to age in both the H (P less than 0.0001) and the OP subjects (P less than 0.01). The rate of bone loss with age was also higher with QCT than with DER in both normal and osteoporotic women. The difference in bone density between the H and the OP subjects was larger (P less than 0.05) with QCT than with DER. Receiver operating characteristic analysis revealed that QCT was a better predictor of vertebral fractures than DER. A larger percentage of OP subjects were 2 SD or more below the normal predicted value with QCT (41%) than with DER (29%). Furthermore, the slopes of the regressions of bone density with age for normal and osteoporotic women were significantly different (P less than 0.05) with QCT but not with DER. These findings are consistent with a disproportionate loss of trabecular bone with age in osteoporosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Role of eicosanoids as mediators of inflammation in inflammatory bowel disease.

Abstract: An unknown initiating event in inflammatory bowel disease (IBD) activates the immune system, which is followed by infiltration of the intestinal mucosa with inflammatory cells and the production of soluble mediators of inflammation. These mediators of inflammation include the metabolites of arachidonic acid. The results of research on arachidonic acid metabolites are reviewed, and it is concluded that the major arachidonic metabolites in human IBD mucosa are the lipoxygenase products leukotriene B4 (LTB4) and 5-hydroxy-6,8,11,14-eicosatetraenoic acid. These metabolites are found in much higher concentrations in mucosa from patients with IBD than from healthy controls. Significantly more chemotactic activity is found in IBD mucosa than in healthy mucosa, and most of this activity is attributable to LTB4. Enhanced synthesis of LTB4 could account for much of the inflammatory response in IBD. Inhibition of the lipoxygenase pathway could be the mechanism that accounts for the therapeutic efficacy of mesalazine.

Prospective study of long-term pulmonary manifestations of mantle irradiation.

Abstract: Given the high cure rate of patients with Hodgkin's disease, the complications related to therapy take on great significance. Mantle irradiation to the thorax is used in virtually all patients with early stage Hodgkin's disease. Prior studies of patients receiving mantle irradiation demonstrated short-term (up to 24 months) abnormalities of pulmonary function. In the present study, we prospectively studied 13 patients for up to 60 months after irradiation only with serial pulmonary function tests, arterial blood gas tests, diffusing capacity of carbon monoxide, chest radiographs, and ventilation-perfusion scans. No respiratory symptoms attributable to therapy were noted. Frequent radiographic changes (62%) were found consisting of apical fibrosis, paramediastinal fibrosis, or pleural thickening. Two patients developed an asymptomatic spontaneous pneumothorax that resolved with conservative management. Ventilation-perfusion scans often (73%) revealed decreased perfusion to the lung apices with associated ventilatory deficits in one-half of these patients. Patients with intrathoracic disease had decreased lung volumes prior to therapy, and lung volumes did not change following irradiation. Lung mechanics were normal throughout the study. Gas exchange at rest was normal in patients with extrathoracic disease. Patients with intrathoracic disease often presented with an abnormal arterial PO2 and widened alveolar-arterial partial pressure gradient for oxygen. However, these parameters normalized by 9 months after therapy. Despite the frequent development of radiographic and V/Q scan abnormalities in the lung apices, patients tolerated mantle radiotherapy remarkably well. In fact, patients with intrathoracic disease demonstrated improved gas exchange at rest following therapy.

Extracellular matrix receptors in the kidney cortex.

Abstract: Extracellular matrix (ECM) receptors anchor cells to substratum and impart positional information to cells. Within the group of ECM receptors known as integrins, alpha-subunits of these alpha beta ...

Discerning the latent structure of hypothetical psychosis proneness through admixture analysis

Abstract: The application of psychometric procedures to a normal population sample to detect individuals with increased liability for schizophrenia is a useful methodological adjunct to the traditional genetic high-risk strategy. A necessary and reasonable step in the process of establishing the utility of a viable psychometric index of schizotypy is the formal investigation of the latent structure of psychometric values. The present study used admixture analysis to examine the distribution of scores on the Perceptual Aberration Scale (PAS), an objective measure of hypothetical psychosis-proneness, in a randomly ascertained sample of 18-year-old university students (n = 707). We applied parametric methods that assumed normally distributed component distributions; viewed in this context, our results are hypothesis-generating and not definitive confirmation of specific hypotheses. Within our methodological framework, the results provide strong evidence for the commingling of normal distributions, even after allowing for unequal variances across components and after removing skewness. The overall distribution of power-transformed data is consistent with the existence of three qualitatively distinct classes of PAS responders. We discuss our results in light of Meehl's model of schizotaxia, a "mixed model" of inheritance of liability to schizophrenia, and we review the methodological implications of our findings for future research.

Sexual concerns after heart transplantation.

Abstract: Sexual concerns after heart transplantation are commonly experienced yet seldom voiced. Forty-five patients approved for this procedure were surveyed regarding sexual issues. Twenty-one (47%) persons responded, of whom 16 had undergone heart transplantation, and five were waiting for a donor. Sexual dysfunction included impotence, ejaculation problems, altered libido, and avoidance of sexual opportunities. Contributing factors to these sexual difficulties were fear of death during coitus, effects of medication on interest and ability to function, body-image concerns, depression, uncertainty about the sexuality of the donor, and altered roles and responsibilities within the family. Recommendations for members of heart transplant teams include (1) obtaining a routine sexual history during the evaluation of candidates, (2) heightening awareness of the sexual concerns of these persons, (3) aggressively treating clinical depression, (4) establishing peer support groups for spouses of transplant patients, (5) presenting didactic material on sexual issues after transplant, (6) adjusting medications when sexual problems arise, and (7) addressing one's own level of comfort in discussing sex-related topics with transplant patients.

HLA antigens in lichen sclerosus et atrophicus.

Abstract: • Several reports have found conflicting data regarding the association between lichen sclerosus et atrophicus (LSA) and HLA types. Association with HLA-A31 and -B40 has been noted, whereas another report found no correlation. We are the first to specifically examine HLA types in white patients in the United States. We have found a significant association between LSA and HLA-A29 and -B44 individually and an even stronger association with the combination of A29 and B44. A review of previous LSA-HLA studies, as well as several reports of HLA typing in familial LSA, is discussed, with consideration given to possible reasons for the discrepancies among the various studies. ( Arch Dermatol. 1990;126:1043-1045)

Antacid and sucralfate-induced hypophosphatemic osteomalacia: a case report and review of the literature.

Abstract: A 42-year-old woman presented to our institution with a 2-week history of bone pain in the lower extremities. Her history was remarkable for duodenal ulcer and long-term treatment with a magnesium-aluminum hydroxide antacid (Maalox) and sucralfate. Initial laboratory studies showed severe hypophosphatemia and elevated alkaline phosphatase and serum 1,25-dihydroxyvitamin D levels. Bone scan showed multiple areas of increased uptake consistent with osteomalacia and microfractures. The patient recovered completely following withdrawal of antacids and sucralfate and short-term treatment with phosphate. Although hypophosphatemia induced by aluminum-containing antacids is rare, treatment of peptic ulcer disease with a combination of two aluminum-containing agents may increase the risk of clinically significant hypophosphatemia. Awareness of this condition is important, because early recognition can prevent morbidity and lead to safe and effective treatment.

A peripheral mechanism preserves self-tolerance to a secreted protein in transgenic mice.

Abstract: We have examined mechanisms of tolerance to circulating self-proteins in mice that are transgenic for human insulin. Normal, nontransgenic mice develop serum antibody responses when injected with human insulin in CFA; syngeneic transgenic mice do not. B cell responsiveness was assessed by immunizing with human insulin coupled to a T-independent Ag, Brucella abortus. No differences were found in the numbers of insulin-specific splenic plaque-forming cells between transgenic and nontransgenic mice suggesting that insulin-specific B cells are not tolerant in transgenic mice. Similarly, APC from transgenic and nontransgenic mice display no differences in their ability to process and present human insulin to human insulin-specific T cells in vitro. However, marked differences were detected between transgenic and nontransgenic T cells. Lymph node T cells from transgenic mice primed with human insulin provided no detectable helper activity for secondary antibody responses to human insulin whereas, lymph node T cells from nontransgenic mice did. Nevertheless, lymph node T cells from transgenic mice developed significant proliferative responses to human insulin. Lymph node T cells obtained from transgenic and nontransgenic mice were fused to BW5147 and human insulin-specific T cell hybridomas were generated. The fact that human insulin-specific T cell hybridomas were obtained from the transgenic mice suggests that these T cells were not clonally deleted. In addition, APC from transgenic mice did not stimulate human insulin-specific hybridomas from normal mice in the absence of exogenous insulin. We suggest that T cells specific for human insulin are not deleted in the thymus of transgenic mice because APC in the thymus do not bear the requisite levels of endogenous human insulin/Ia complexes. Therefore, we conclude that tolerance in the transgenic mice is preserved by peripheral mechanisms.

Solvent use and psychiatric comorbidity

Abstract: From a family study of 286 alcoholics, 157 felons, 60 control subjects, and 1640 of their relatives, 130 solvent users were retrospectively identified. Risk for diagnosis of antisocial personality disorder was significantly elevated for all solvent users. Relatives, though not probands, were more likely to receive diagnoses of alcoholism and secondary depression, but this relationship appeared to be mediated by the presence of antisocial personality disorder. Solvent users were not at increased risk for primary depression or other psychiatric illnesses. Subjects reporting any solvent use also had significantly increased risk of suicidal ideation and suicide attempt compared to non-users, with half of the solvent users reporting suicidal ideation and 30% reporting a history of suicide attempt. However, risk for suicidal ideation and suicide attempt among solvent users appeared to covary with presence of antisocial personality disorder, alcoholism, and secondary depression rather than being specifically associated with solvent use.

Transmission of a psychometric indicator for liability to schizophrenia in normal families.

Abstract: The genetic analysis of schizophrenia would be facilitated by identification of a heritable correlate of liability Deviance on an index of Minnesota Multiphasic Personality Inventory (MMPI) signs is associated with the disease phenotype; the familial aggregation and mode of transmission of this continuous psychometric indicator have yet to be established In this paper, we examine the indicator through commingling analysis and segregation analysis with both the mixed and unified models on 65 nuclear families containing 211 normal individuals Evidence for a high degree of familiality is found Analysis of untransformed data under a conditional likelihood provides evidence for Mendelian transmission of a major gene with commingling of two distributions The frequency of the "high index score" allele is 015, with the gene accounting for 31% of the total population variance; such a locus would be relevant to the study of psychopathology as 28% of the population would carry at least one deviant allele When power-transformed scores are used to eliminate skewness, there is evidence for one distribution and it is not possible to distinguish single gene from multifactorial (polygenic or cultural) inheritance While our findings regarding mode of transmission must be interpreted cautiously and confirmation of a single locus requires further study, demonstration of familiality warrants continued investigation of the index as an indicator of liability for schizophrenia

Boron neutron capture enhancement of 252Cf brachytherapy.

Abstract: Dosimetric and radiobiological studies were undertaken to investigate the potential enhancement in dose, dose distribution and cell killing effectiveness of 252Cf brachytherapy achievable when boron-10 enriched compounds are incorporated into simulated 252Cf brain implants. Thermal neutron distributions in a human head phantom containing a 252Cf source were measured by gold foil activation and calculated using a 1-dimensional transport code. This information was then used to modify measured event size distributions for 252Cf neutrons to determine the corresponding increase in dose and dose equivalent throughout the phantom. The addition of subtoxic levels of boron-10 to a typical 252Cf implant was found to significantly enhance both the absorbed dose and the high LET event frequency at distances of 3 to 5 cm from individual sources. Some unexpected geometric considerations are discussed. Reduced survival of cultured Chinese hamster cells correlated with the predicted increase in absorbed dose from the capture events with a concentration of about 60 micrograms 10B per ml in the culture medium. It was found that boron increased alpha (the "single-hit" parameter of the linear quadratic survival model) by 32% and decreased beta (the "double-hit" parameter) by 8%. The alpha/beta ratio increased to 4.34 Gy in the presence of boron, from 3.03 Gy in its absence. This translated to an 8% reduction in californium dose needed to effect 10% cell survival. It is concluded that there is a sufficiently high thermal neutron fluence present during californium brachytherapy for boron neutron capture dose augmentation to be feasible.

Molecular surgery of the basement membrane by the argon laser.

Abstract: Although the argon laser is used successfully to weld a number of different tissues, the underlying chemical and cellular mechanisms for this process are not precisely defined. Consequently, a biochemical model has been developed in vitro using the welldefined extracellular matrix from the murine Engelbreth-Holm-Swarm (EHS) sarcoma. Control and experimental samples of EHS basement membranes were irradiated with a Trimedyne argon laser at 500–3,000 Joules/cm2 at 0°C. The samples were diluted into cold phosphate-buffered saline and allowed to gel at 35°C. The time course of the gelation reaction was followed in a spectrophotometer at 360 nm. Irradiation reduced the absorbance 7.5–15% compared to controls and was independent of the dilution over a 10-fold range. Gelation was also measured by determining the amount of protein by the Bradford assay that could be collected by centrifugation at 10,000g for 10 minutes. Argonirradiated samples had 30–40% less protein in the precipitate than the controls. The addition of 5 mM beta-mercaptoethanol to the EHS extract blocked the effect of the laser on the gelation reaction. In addition, when gelation was carried out in the absence of calcium and magnesium, there were no differences between laser-treated samples and controls. The basement membrane proteins were separated by electrophoresis through polyacrylamide gels under denaturing plus reducing or denaturing and non-reducing conditions. No differences in the polypeptide composition were noted between irradiated and control samples using either Coomassie- or silver-staining techniques. The irradiated and control samples were also analyzed on 1.5% agarose gels in 10 mm Tris-HCl, pH 8 containing 0.1% SDS. Both samples produced a single Coomassie-positive band, but the control migrated at 0.5 and the irradiated sample at 0.6. In sum, the conformation of extracellular matrix proteins can be altered by the argon laser at welding energies at low temperatures, even though no new covalent interactions were observed.

Mammalian pancreatic cholesterol esterase

Abstract: The invention provides methods for the purification to homogeneity of pancreatic cholesterol esterase in useful quantities from a variety of mammalian species. The gene for a mammalian pancreatic cholesterol esterase has been cloned and sequenced, and is useful for expressing cholesterol esterase in a transformed eukaryotic or prokaryotic cell culture. Thus, methods according to the invention enable the production of large quantities of pancreatic cholesterol esterase for the screening of inhibitors, the production of antibodies, and for commercial purposes related to the alteration of cholesterol/cholesterol ester composition of materials containing free or esterified cholesterol.

Pseudoaneurysm: diagnosis with color Doppler ultrasound.

Abstract: Increasing numbers of interventional radiologic procedures, often with large arterial catheters, have led to increasing total numbers of complications. Pseudoaneurysm is not an infrequent complication. It is often difficult to differentiate pseudoaneurysm clinically from hematoma. In the past, we have used gray scale duplex scanning to aid in this differentiation. We have recently found color Doppler scanning to allow quicker, easier, and more accurate diagnosis. Color Doppler imaging also can often demonstrate the track between the artery and the aneurysm.

Criteria for Classifying Breast Cyst Fluids

Abstract: Since the scheme was first proposed by Bradlow et al.,' the use of electrolyte composition has been generally recognized to be useful in classifying cyst fluids. Unfortunately, there has been no agreement on the precise concentrations to be used as cutoff values for the different classes. Some laboratories have used simple concentrations; others have used ratios or logs of ratios. This had led to confusion because the classes from different laboratories overlap in different ways. Although when the original suggestion was made the physiological basis for the difference in electrolyte composition was not known, we now have several suggestions for the biochemical mechanism. In order to facilitate consistent classification by all groups, it seems desirable to develop a consensus classification based on physiological grounds. In fact, each of the physiological grounds points to the same criteria for distinguishing the classes: Bradlow et al.,' Miller et al.,' and Dogliotti et aL3 recognized that there are two patterns of electrolytes. One pattern with high K+ concentrations and low Na+ and C1(designated as type 1) and a second pattern with low Kf and high Na+ and C1concentrations (designated as type 2). Cutoff values, however, were different among the above-cited groups. The inverse relationship between K + and C1was recognized by all of the groups, yet only Bradlow el al. pointed out cutoff values for C1that could be used to identify the different classes of cyst fluids: A certain number of fluids were found to have an intermediate pattern, designated as type 3. Molina suggested that cysts may be classified as transudative or secretory in terms of their electrolyte characteristics? The transudative cysts had electrolyte composition

12-[(5-iodo-4-azido-2-hydroxybenzoyl)amino]dodecanoic acid: biological recognition by cholesterol esterase and acyl-CoA:cholesterol O-acyltransferase.

Abstract: Potential probes of protein cholesterol and fatty acid binding sites, namely, 12-[(5-iodo-4-azido-2-hydroxybenzoyl)amino]dodecanoate (IFA) and its coenzyme A (IFA:CoA) and cholesteryl (IFA:CEA) esters, were synthesized. These radioactive, photoreactive lipid analogues were recognized as substrates and inhibitors of acyl-CoA:cholesterol O-acyltransferase (ACAT) and cholesterol esterase, neutral lipid binding enzymes which are key elements in the regulation of cellular cholesterol metabolism. In the dark, IFA reversibly inhibited cholesteryl [14C]oleate hydrolysis by purified bovine pancreatic cholesterol esterase with an apparent Ki of 150 microM. Cholesterol esterase inhibition by IFA became irreversible after photolysis with UV light and oleic acid (1 mM) provided 50% protection against inactivation. Incubation of homogeneous bovine pancreatic cholesterol esterase with IFA:CEA resulted in its hydrolysis to IFA and cholesterol, indicating recognition of IFA:CEA as a substrate by cholesterol esterase. The coenzyme A ester, IFA:CoA, was a reversible inhibitor of microsomal ACAT activity under dark conditions (apparent Ki = 20 microM), and photolysis resulted in irreversible inhibition of enzyme activity with 87% efficiency. IFA:CoA was also recognized as a substrate by both liver and aortic microsomal ACATs, with resultant synthesis of 125IFA:CEA. IFA and its derivatives, IFA:CEA and IFA:CoA, are thus inhibitors and substrates for cholesterol esterase and ACAT. Biological recognition of these photoaffinity lipid analogues will facilitate the identification and structural analysis of hitherto uncharacterized protein lipid binding sites.

Hypotrichosis with spondyloepimetaphyseal dysplasia in three generations: a new autosomal dominant syndrome.

Abstract: We describe a family with a new disorder characterized by congenital hypotrichosis and spondyloepimetaphyseal dysplasia that results in mild rhizomelic short stature. Five individuals in 3 generations are affected with autosomal dominant inheritance.

Biochemical intermediates in α1-Antitrypsin deficiency : residual family resemblance for total α1-Antitrypsin, oxidized α1-Antitrypsin, and immunoglobulin E after adjustment for the effect of the Pi locus

Abstract: alpha 1-antitrypsin (alpha 1 AT) deficiency is variably associated with the development of pulmonary emphysema. To gain insight into the process which begins the Z point mutation at the Protease Inhibitor (Pi) locus and results in the variable development of emphysema, three quantitative phenotypes, including total alpha 1 AT, oxidized alpha 1 AT, and total immunoglobulin E (IgE), were measured in sera from alpha 1-antitrypsin-deficient individuals and their families. The mean and variance effects of the Pi locus on these biochemical phenotypes were removed, and path analysis of the residual phenotypes was performed by using a TAU model to investigate whether there was any additional multifactorial transmission. Significant transmission was demonstrated for total serum IgE and serum-oxidized alpha 1 AT, which could be due to major genes other than the Pi locus, polygenes, or familial environment. Segregation analysis of the residual phenotypes was performed to determine whether additional major gene effects, other than the Pi effect, influence these quantitative phenotypes. Convincing evidence for an additional major gene was not found for oxidized alpha 1 AT, total alpha 1 AT, or IgE.

Effect of ketoconazole on plasma sex hormones, lipids, lipoproteins, and apolipoproteins in hyperandrogenic women

Abstract: The aim of the current study of 18 hyperandrogenic women was to determine the affects of ketoconazole (KTZ), an oral synthetic antifungal imidazole derivative that inhibits gonadal and adrenal steroidogenesis, on lipids, lipoprotein cholesterols, apolipoproteins, endogenous sex steroid hormones, and their interactions. Eighteen hyperandrogenic women, ages 18 to 35, with a history of severe acne and/or hirsutism, were randomly divided into two groups of nine, both receiving KTZ (group 1,400 mg/d; group 2,800 mg/d) for 10 days. In groups 1 and 2, KTZ therapy reduced cholesterol (10%, P ≤ .01; 19%, P ≤ .05) and low-density lipoprotein (LDL)-cholesterol (13%, P ≤ .05; 33%, P ≤ .025), and increased apoplipoprotein (apo) A1 (7%, P ≤ .005; 13%, P ≤ .01). KTZ, 800 mg/d, decreased apo B (21%, P ≤ .005), and lowered the ratio of LDL-cholesterol to high-density lipoprotein (HDL)-cholesterol (40%, P ≤ .01). KTZ therapy more than doubled the levels of estradiol (E2) in both groups (136%, P ≤ .01; 171%, P ≤ .01) and, in the high-dose group, decreased the levels of free testosterone (FT) (48%, P ≤ .05) and dehydroepiandrosterone-sulfate (DHEA-S) (36%, P ≤ .005). The reductions of total and LDL-cholesterol appear to be attributable to the increases in E2 and possibly to the decrease in FT. KTZ therapy may have beneficial effects on atherogenic lipid and lipoprotein patterns in women with hyperandrogenicity.